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Complement C5a, a potent anaphylatoxin, is a candidate target molecule for the treatment of inflammatory diseases, such as myocardial ischemia/reperfusion injury, RA, and the antiphospholipid syndrome. In contrast, up until now, no specific contribution of C5a and its receptor, C5aR, was recognized in diseases of antibody-dependent type II autoimmunity. Here we identify C5a as a novel key mediator of autoimmune hemolytic anemia (AIHA) and show that mice lacking C5aR are partially resistant to this IgG autoantibody–induced disease model. Upon administration of anti-erythrocyte antibodies, upregulation of activating Fcγ receptors (FcγRs) on Kupffer cells, as observed in WT mice, was absent in C5aR-deficient mice, and FcγR-mediated in vivo erythrophagocytosis was impaired. Surprisingly, in mice deficient in FcγRI and FcγRIII, anti-erythrocyte antibody–induced C5 and C5a production was abolished, demonstrating the existence of a previously unidentified FcγR-mediated C5a-generating pathway. These results show that the development of a full-blown antibody-dependent autoimmune disease requires C5a — produced by and acting on FcγR — and may suggest therapeutic benefits of C5 and/or C5a/C5aR blockade in AIHA and other diseases closely related to type II autoimmune injury.

Blood samples from 65 patients with primary Sjögren's syndrome were evaluated for the presence of antiphospholipid antibodies. Increased levels of antiphospholipid antibodies were found in 13 of 65 (20%) of patients. These antiphospholipid antibodies were predominantly of the IgA isotype, in contrast with the IgG isotype antiphospholipid antibodies found in patients with systemic lupus erythematosus (SLE). The presence of IgA antiphospholipid antibodies in the patients with primary Sjögren's syndrome was not significantly associated with arterial or vascular thrombosis, nor peripheral or central nervous system vasculitis. There was no association with laboratory determined features such as lupus anticoagulant or false positive results of the Venereal Disease Research Laboratory (VDRL) test. Oligonucleotide specific DNA amplification and hybridisation with allele specific probes was used to examine the HLA-D antigens occurring in this group of patients with primary Sjögren's syndrome. Of 13 patients with antiphospholipid antibodies, seven had the genotype HLA-DR2/DR3. However, compared with the whole group of 65 patients with Sjögren's syndrome, no increased occurrence of haplotype DR2 or DR3 was noted. These results suggest that gene interaction between DR2 and DR3 may play a part in the production of antiphospholipid antibodies in patients with Sjögren's syndrome. In contrast with patients with SLE, the IgA antiphospholipid antibodies in patients with Sjögren's syndrome are not risk factors for thrombosis or vasculitis. The presence of IgA antiphospholipid antibodies in patients with Sjögren's syndrome probably reflects its production at mucosal sites of inflammation and the absence of vasculopathy may be due to the inability of IgA antibodies to activate complement.

Thrombotic microangiopathic hemolytic anemia (TMHA) is not uncommon in clinical nephrology practice while antiphospholipid syndrome (APS) is uncommon. Although less than 1% of patients with APS develop catastrophic APS (CAPS), its potential lethal outcome because of thrombosis in multiple organs and subsequent multiorgan failure emphasizes its importance in nephrology practice. Here is a case of catastrophic APS in a 7-year-old girl, who presented to us with TMHA associated with antiphospholipid antibodies and subsequently died because of CAPS.

A patient with warm autoimmune hemolytic anemia (AIHA) due to predominance of immunoglobulin A (IgA) with an Rh specificity, considered to be the first case in Korea, is described. A 13-year-old male patient with severe hemolytic anemia showed a weak reactivity (1+) in the direct antiglobulin test (DAT) by using anti-IgG antiglobulin reagent. This finding, however, could not fully explain the patient's severe AIHA. When anti-IgA reagent was used for the DAT, strong reactivity (4+) was observed and free anti-E and anti-c autoantibodies were also detected by anti-IgA and anti-IgG reagents. The patient's hemoglobin began to rise with the administration of steroids. Because RBCs coated with multiple types of immunoglobulins are associated with more severe hemolysis than those only with IgG, the DATs using anti-IgA and other reagents are needed for the correct diagnosis when the result of DAT is not compatible with patient's clinical manifestations.

Wiskott–Aldrich Syndrome (WAS) is a severe X-linked Primary Immunodeficiency that affects 1–10 out of 1 million male individuals. WAS is caused by mutations in the WAS Protein (WASP) expressing gene that leads to the absent or reduced expression of the protein. WASP is a cytoplasmic protein that regulates the formation of actin filaments in hematopoietic cells. WASP deficiency causes many immune cell defects both in humans and in the WAS murine model, the Was−/− mouse. Both cellular and humoral immune defects in WAS patients contribute to the onset of severe clinical manifestations, in particular microthrombocytopenia, eczema, recurrent infections, and a high susceptibility to develop autoimmunity and malignancies. Autoimmune diseases affect from 22 to 72% of WAS patients and the most common manifestation is autoimmune hemolytic anemia, followed by vasculitis, arthritis, neutropenia, inflammatory bowel disease, and IgA nephropathy. Many groups have widely explored immune cell functionality in WAS partially explaining how cellular defects may lead to pathology. However, the mechanisms underlying the occurrence of autoimmune manifestations have not been clearly described yet. In the present review, we report the most recent progresses in the study of immune cell function in WAS that have started to unveil the mechanisms contributing to autoimmune complications in WAS patients.

Autoimmune hemolytic anemia associated with an ovarian teratoma is a very rare disease. However, treating teratoma is the only method to cure the hemolytic anemia, so it is necessary to include ovarian teratoma in the differential diagnosis of autoimmune hemolytic anemia. We report herein on a case of a young adult patient who had severe autoimmune hemolytic anemia that was induced by an ovarian teratoma. A 25-yr-old woman complained of general weakness and dizziness for 1 week. The hemoglobin level was 4.2 g/dL, and the direct and indirect antiglobulin tests were all positive. The abdominal computed tomography scan revealed a huge left ovarian mass, and this indicated a teratoma. She was refractory to corticosteroid therapy; however, after surgical resection of the ovarian mass, the hemoglobin level and the reticulocyte count were gradually normalized. The mass was well encapsulated and contained hair and teeth. She was diagnosed as having autoimmune hemolytic anemia associated with an ovarian teratoma. To the best of our knowledge, this is the first such a case to be reported in Korea.

Introduction

Antiphospholipid syndrome is an autoimmune disorder characterized by either a history of vascular thrombosis (one or more clinical episodes of arterial, venous, or small vessel thrombosis in any tissue or organ) or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The systemic features of the syndrome are characterized by large variability depending on the affected organ(s). Among them, neurological and behavioural disturbances, dermatological features as livedo reticularis and renal, ocular, liver or valvular heart manifestations have been reported in antiphospholipid syndrome patients. However, studies on the frequency and clinical presentation of the ocular manifestations as the prevailing (first) sign of antiphospholipid syndrome in patients suffering from "unexplained" ocular disease are missing. Herein, we present three cases suffering from unexplained ocular disease as first manifestation of antiphospholipid syndrome.

Case presentation

All the three patients were referred to our department because of unexplained ocular features from the anterior or posterior segment and unexplained neuro-ophthalmologic symptoms. The first patient had bilateral retinal occlusive disease, the second and the third patient had unilateral nonarteritic anterior ischemic optic neuropathy with macular oedema. Moderate to high levels of antiphospholipid antibodies were detected in all of them at baseline as well as 6 to 12 weeks after initial testing confirming the presence of antiphospholipid antibodies. Anticoagulant treatment with acenocoumarol was instituted resulting in stabilization and/or improvement of ocular signs in all of them.

Conclusion

Due to the important diagnostic and therapeutic implications of antiphospholipid syndrome, the possibility of ocular features as the first clinical manifestation of antiphospholipid syndrome should be kept in mind of the physicians particularly in patients with no evident risk factors for ocular disease. In this case, prompt anticoagulant treatment and close follow-up seem to be essential for vision salvation and stabilization.

Warm antibody autoimmune hemolytic anemia is due to the presence of warm agglutinins that react with protein antigens on the surface of red blood cells causing premature destruction of circulating red blood cells. We report the first case of concurrent reactive arthritis, Graves’ disease, and autoimmune hemolytic anemia. A 40-year-old man with reactive arthritis, Graves’ disease, type 2 diabetes mellitus, mitral valve prolapse, and Gilbert’s disease presented with a one month history of jaundice, fatigue, and black stools. After diagnosis of warm autoimmune hemolytic anemia, the patient was started on prednisone 1 mg/kg with rapid improvement in his anemia and jaundice. Our subject’s mother and possibly his maternal grandmother also had autoimmune hemolytic anemia, which raises the possibility of hereditary autoimmune hemolytic anemia, a rarely reported condition.

Introduction

Idiopathic Autoimmune Hemolytic Anemia is a potentially fatal condition which requires prompt and potent treatment. Diagnosis of idiopathic autoimmune hemolytic anemia requires both serologic evidence of autoantibody presence and hemolysis. Although most of the times it is considered idiopathic, several underlying causes have been identified, like autoimmune and connective tissue diseases, viral infections, drugs or hyper function of the immune system. To our knowledge, this is the first case in the international literature describing lecithin-induced autoimmune hemolytic anemia.

Case Presentation

This case report is to highlight a rare but dangerous adverse reaction to overdose of lecithin. A 38 year old white female from Greece, presented to our emergency room with progressive fatigue over a period of ten days and icteric discoloration of her skin and conjunctiva. The patient had been taking lecithin supplements (1200 mg, 3 capsules a day) over a period of ten days for weight loss. She reports that the last 3 days, prior to the examination, she took 5 capsules/day, so that the supplement would take effect more rapidly. Her past medical, social and family history showed no disturbance. Relatives of the patient were requested to submit any blood-tests taken over a period of 20 days prior to the onset of symptoms caused by Lecithin. All tests proved that all functions were within normal scale. Her physical examination revealed pallor and jaundice without palpable hepatosplenomegaly. Blood biochemistry tests showed total bilirubin 7.5 mg/dl, with indirect bilirubin 6.4 mg/dl and complete blood count showed hemoglobin 7.6 g/dl with blood levels 21.4%.

Conclusion

In every case of idiopathic autoimmune hemolytic anemia the administration of pharmaceutical substances should always be examined, except for the standard reasons that cause it. In this case the cause of hemolysis was attributed to the excessive intake of lecithin capsules for the loss of body weight. It is important that clinicians and immunologists are aware of this adverse effect.

Antiphospholipid syndrome is a disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently elevated levels of antiphospholipid antibodies. It was first described in a group of patients with systemic lupus erythematosus but has since been associated with a wide range of conditions, including other autoimmune disorders and malignancy. It can also occur in isolation, the so-called primary antiphospholipid syndrome. We describe an elderly woman with the antiphospholipid syndrome thought to be associated with a cholangiocarcinoma.


Keywords: antiphospholipid syndrome; cholangiocarcinoma; deep vein thrombosis

Chronic granulomatous disease (CGD) is characterized by recurrent infections and granuloma formation. In addition, we have observed a number of diverse autoimmune conditions in our CGD population, suggesting that patients with CGD are at an elevated risk for development of autoimmune (AI) disorders. In this report, we describe antiphospholipid syndrome (aPL), recurrent pericardial effusion, juvenile idiopathic arthritis (JIA), IgA nephropathy, cutaneous lupus erythematosus, and autoimmune pulmonary disease in the setting of CGD. The presence and type of autoimmune disease has important treatment implications for patients with CGD.

Background

The clinical utility of testing for antiphospholipid antibodies (aPL) of IgA isotype remains controversial.

Methodology/Principal Findings

To address this issue, we reasoned that if IgA aPL contribute to the clinical manifestations of the antiphospholipid syndrome, then an association with thromboembolic events should manifest in patients whose only aPL is of IgA isotype. We performed a retrospective chart review of 56 patients (31 with systemic lupus erythematosus [SLE] and 25 without SLE) whose only positive aPL was IgA anti-β2-glycoprotein I (isolated IgA anti-β2GPI) and compared their clinical features with 56 individually matched control patients without any aPL. Patients with isolated IgA anti-β2GPI had a significantly increased number of thromboembolic events, as compared to controls. When patients were stratified into those with and without SLE, the association between isolated IgA anti-β2GPI and thromboembolic events persisted for patients with SLE, but was lost for those without SLE. Titers of IgA anti-β2GPI were significantly higher in SLE patients who suffered a thromboembolic event. Among patients with isolated IgA anti-β2GPI, there was an increased prevalence of diseases or morbidities involving organs of mucosal immunity (i.e., gastrointestinal system, pulmonary system, and skin).

Conclusions/Significance

The presence of isolated IgA anti-β2GPI is associated with an increased risk of thromboembolic events, especially among patients with SLE. IgA anti-β2GPI is associated with an increased prevalence of morbidities involving organs of mucosal immunity.

Antiphospholipid syndrome is a systemic autoimmune disease with thrombotic tendency. Consensus guidelines for pregnancy with antiphospholipid syndrome recommend low-dose aspirin combined with unfractionated or low-molecular-weight heparin because antiphospholipid syndrome causes habitual abortion. We report a 36-year-old pregnant woman diagnosed with antiphospholipid syndrome receiving anticoagulation treatment. The patient developed left abdominal pain and gross hematuria at week 20 of pregnancy. An initial diagnosis of left ureteral calculus was made. Subsequently abdominal-pelvic computed tomography was required for diagnosis because of the appearance of severe contralateral pain. Computed tomography revealed serious renal hemorrhage, and ureteral stent placement and pain control by patient-controlled analgesia were required. After treatment, continuance of pregnancy was possible and vaginal delivery was performed safely. This is the first case report of serious renal hemorrhage in a pregnant woman with antiphospholipid syndrome receiving anticoagulation treatment and is an instructive case for urological and obstetrical practitioners.

Introduction

Mixed warm and cold autoimmune hemolytic anemia runs a chronic course with severe intermittent exacerbations. Therapeutic options for the treatment of hemolysis associated with autoimmune hemolytic anemia are limited. There have been only two reported cases of the effective use of rituximab in the treatment of patients with mixed autoimmune hemolytic anemia. We report a case of severe mixed autoimmune hemolytic anemia that did not respond to steroids and responded to four weekly doses of rituximab (one cycle).

Case presentation

A 62-year-old Caucasian man presented with dyspnea, jaundice and splenomegaly. His blood work revealed severe anemia (hemoglobin, 4.9 g/dL) with biochemical evidence of hemolysis. Exposure to cold led to worsening of the patient's hemolysis and hemoglobinuria. A direct antiglobulin test was positive for immunoglobulin G and complement C3d, and cold agglutinins of immunoglobulin M type were detected. A bone marrow biopsy revealed erythroid hyperplasia. A positron emission tomographic scan showed no sites of pathologic uptake. There was no other evidence of a lymphoid or myeloid disorder. Initial therapy consisted of avoidance of cold, intravenous methylprednisolone and a trial of plasmapheresis. However, there was no clinically significant response, and the patient continued to be transfusion-dependent. He was then started on 375 mg/m2/week intravenous rituximab therapy. After two treatments, his hemoglobin stabilized and the transfusion requirement diminished. Rituximab was continued for a total of four weeks and led to the complete resolution of his hemolytic anemia and associated symptoms. At the patient's last visit, about two years after the initial rituximab treatment, he continued to be in complete remission.

Conclusion

To the best of our knowledge, this is the first reported case of mixed-type autoimmune hemolytic anemia that did not respond to steroid therapy but responded completely to only one cycle of rituximab. The previous two reports of rituximab use in mixed autoimmune hemolytic anemia described an initial brief response to steroids and the use of rituximab at the time of relapse. In both of these case reports, the response to one cycle of rituximab was short-lived and a second cycle of rituximab was required. Our case report demonstrates that severe hemolysis associated with mixed autoimmune hemolytic anemia can be unresponsive to steroid therapy and that a single cycle of rituximab may lead to prompt and durable complete remission.

Interferon-beta is widely used for the treatment of relapsing multiple sclerosis. The drug is usually well tolerated, but autoimmune adverse effects, including kidney disease, have been reported. Only a few cases of hemolytic uremic syndrome-thrombotic microangiopathy associated interferon-alpha have been described so far, and even fewer with beta-interferon. We report a patient who developed thrombotic microangiopathy during treatment with interferon-beta and improved after discontinuation and steroid therapy. Complement cascade and antiphospholipid antibodies are investigated. The spectrum of renal diseases associated with interferon-beta treatment is also reviewed.

OBJECTIVES--To determine whether active immunisation of mice with pathogenic anticardiolipin antibodies (IgG and IgM), derived from the serum of a patient with the antiphospholipid syndrome, could dysregulate the idiotypic cascade and induce the production of anti-anti-anti-cardiolipin (Ab3) with anticardiolipin activity by the mice with the association of overt antiphospholipid syndrome. METHODS--Anticardiolipin antibodies were purified from the serum of a patient with the antiphospholipid syndrome. The purified anticardiolipin antibodies were used to immunise mice at the footpads and the mice were then followed up for serological and clinical manifestations of the antiphospholipid syndrome. RESULTS--The IgG anticardiolipin antibody was found to be monospecific and to bind cardiolipin with high affinity. Immunisation of naive BALB/c mice with the purified IgG anticardiolipin antibody was followed by production in the mice of sustained high titres of IgG anticardiolipin antibody, associated with a prolonged activated partial thromboplastin time (64.5 (9.7) v 30.1 (1.7) seconds in control mice) and thrombocytopenia (0.4 (0.06) x 10(9) v 1.0 (0.09) x 10(9)/l platelets in controls). The titres of other autoantibodies (for example, antibodies to DNA, histone), though high after the immunisation, decreased rapidly and were almost undetected one month after the boost injection. The mice immunised with the IgG anticardiolipin antibody showed low fecundity (36% of mice became pregnant v 62% in the group immunised with control IgG). The pregnant mice had an increased resorption rate (the equivalent of fetal loss in the human) of 61 (9)% v 5 (4)% in the control group. The mean (SD) embryo and placental weights in mice with the antiphospholipid syndrome were significantly lower than in the mice injected with control IgG (641 (210) and 103 (14) mg v 1303 (105) and 145 (8) mg respectively. The IgM anticardiolipin antibodies purified from the same patient were found to be polyspecific, binding with low affinity to anticardiolipin antibodies and double stranded DNA, and carried the anti-DNA idiotype 16/6. Mice immunised with the purified IgM anticardiolipin antibodies, though showing reduced fecundity (30%), had only a slightly increased resorption rate (12 (9) v 3 (5)% in controls) and only a slight and statistically non-significant decrease in mean (SD) embryo and placental weights (1134 (188) and 136 (11) mg respectively). CONCLUSIONS--The results confirm the induction of pathogenic anticardiolipin antibodies by immunisation with serum anticardiolipin, dysregulating the idiotypic network, and point to the higher pathogenic potential of serum IgG v IgM anticardiolipin antibodies.

Here we report the case of a 20-year-old female patient previously diagnosed with Hashimoto's thyroiditis and overt hypothyroidism, and who had been taking synthetic thyroxine (100 µg/day) for eight months. She experienced intermittent dizziness and generalized weakness, and was diagnosed as having severe autoimmune hemolytic anemia (AIHA). We prescribed prednisolone treatment and continued synthetic thyroxine administration. Two years and five months later, she developed idiopathic thrombocytopenic purpura (ITP) and was diagnosed with Evans' syndrome. Thereafter, laparoscopic splenectomy was performed because her autoimmune hemolytic anemia was refractory and dependent on steroid therapy. The HLA genotypes of the patient were HLA-A*020101/A*2602, HLA-B*270502/B*5401, HLA-Cw*0102/Cw*020202, HLA-DRB1*0404/DRB1*0405, and HLA-DQB1*0302/DQB1*0401. Hashimoto's thyroiditis is often associated with other nonendocrine autoimmune diseases, and antithyroid antibodies are frequently observed in Evans' syndrome (coexistence of AIHA and ITP). However, there is no report of Evans' syndrome developing in patients with overt hypothyroidism and Hashimoto's thyroiditis. This case suggests that three autoimmune diseases (AIHA, ITP, and Hashimoto's thyroiditis) might share a common immunogenetic pathway in pathogenesis.

Common variable immunodeficiency (CVID) is the most common clinically significant primary immune defect. Although the hallmark of CVID is hypogammaglobulinemia, the intrinsic dysregulation of the immune system leads to defective T-cell activation and proliferation, as well as dendritic cell and cytokine defects. Although 70% to 80% of patients have had recurrent sinopulmonary infections, auto-immunity and inflammatory complications are also common. The most common autoimmune conditions are immune thrombocytopenic purpura and hemolytic anemia, but other autoimmune complications arise, including rheumatoid arthritis, pernicious anemia, primary biliary cirrhosis, thyroiditis, sicca syndrome, systemic lupus, and inflammatory bowel disease. Treatment of autoimmunity includes high-dose immunoglobulins, corticosteroids, selected immunosuppressants, and other immune modulators. This review focuses on autoimmune conditions associated with CVID, potential mechanisms of immune dysregulation, and therapeutic strategies.

Antiphospholipid syndrome is a systemic autoimmune disease associated with thrombosis and recurrent fetal loss in the setting of detectable antiphospholipid (aPL) antibodies. The major antigenic target has been identifed as β2-glycoprotein I (β2GPI), which mediates binding of aPL antibodies to target cells including endothelial cells, monocytes, platelets and trophoblasts, leading to prothrombotic and proinfammatory changes that ultimately result in thrombosis and fetal loss. This article summarizes recent insights into the role of β2GPI in normal hemostasis, interactions between aPL antibodies, β2GPI and cell-surface molecules, molecular prothrombotic and proinfammatory changes induced by aPL antibodies and pathogenic changes leading to fetal loss in antiphospholipid syndrome. New directions in therapy using these insights are examined.

Background

Common variable immunodeficiency (CVID) is a condition characterized by antibody deficiency, and therefore susceptible to recurrent pyogenic infections, cancer and autoimmune diseases. It is a heterogeneous syndrome in primary immunodeficiencies and clinically the most important is often diagnosed in adulthood. Autoimmunity occurs in 5% of the general population, in patients with CVID the percentage increased to 20 to 48%, cytopenias being the most common cause of autoimmunity in these patients. Autoimmune thrombocytopenic purpura and autoimmune hemolytic anemia are the most common autoimmune consequences, occurring in 5% to 8% of all patients with CVID. Some patients develop these disorders before the diagnosis of CVID.

Methods

We present the case of a woman of 45 year old, with a history of lower respiratory tract and urinary tract infections in recurrent Pulmonary Tuberculosis. Enter the program short-course treatment strictly supervised for pulmonary tuberculosis with appropriate response. Autoinmune thrombocytopenic purpura refractory to steroids (WWTP) for performing splenectomy.

Results

Anti DNA antibodies, anti nuclear, anti-protease, C. ANCA/PR3 antimieloperoxidasa, serology for hepatitis B, C, HIV negative. Serum immunoglobulins were as follow: IgG, 158 mg/dL (normal 700 to 1600), IgM, 55 mg/dL (normal 40–230), IgA, 36 mg/dL (normal 70–400), and, IgE, 38.7 IU/mL (normal 0–100) in more than 2 occasions with values below 2 standard deviations. CD4 T lymphocytes (19%) CD4/CD8 ratio (0.54).

Conclusions

Meets diagnostic criteria for Common Variable Immunodeficiency (CVID) and starting treatment with intravenous immunoglobulin at a dose of 400 mg/kg (every 21 days) with significant clinical improvement and has even managed to integrate into your daily activities. Today, he continues with danazol for WWTP. Therefore, CVID is necessary to consider in the differential diagnosis of autoimmune thrombocytopenic purpura and autoimmune hemolytic anemia in adults (1).

Purpose: Autoimmune factors are involved in some of the cases of reproductive failure. The aim of this paper is to discuss the association between autoantibodies and reproductive failure.

Methods: Literature review of autoantibodies associated with reproductive failure.

Results: Several autoantibodies were found in association with such clinical manifestations, mainly in patients having systemic lupus erythematosus or the antiphospholipid syndrome. These autoantibodies include “classical” antiphospholipid antibodies such as anticardiolipin, anti-β2-glycoprotein-I, antiphosphatidylserine, and antiphosphatidylethanolamine. There are also some “nonclassical” antiphospholipid antibodies directed to prothrombin, thromboplastin, or mitochondrial antibodies of M5 type, which were also found in patients with reproductive failure. Moreover, animal models as well as some human studies support a role for other autoantibodies in these clinical manifestations including antithyroglobulin, antilaminin-1, anti-corpus luteum, antiprolactin, anti-poly(ADP-ribose), and lymphocytotoxic antibodies.

Conclusions: Even though there is not enough data currently to support a firm association between some of these autoantibodies and reproductive failure, future studies are likely to help us determine and expand the number of autoantibodies screened in these patients.

Human lysosomes were isolated from normal peripheral blood leukoyctes and characterized by electron microscopy, enzyme analysis, and assays for DNA and RNA. Stored sera from 37 unselected patients with systemic lupus erythematosus (SLE), including active and inactive, treated and untreated cases, were tested in complement fixation (CF) reactions with these lysosome preparations. 23 SLE sera exhibited positive CR reactions, as did sera from two patients with "lupoid" hepatitis. The seven SLE sera with strongest CF reactivity also demonstrated gel precipitin reactions with lysosomes. Neither CF nor precipitin reactions with lysosomes were observed with normal sera or with sera of patients with drug-induced lupus syndrome, rheumatoid arthritis (RA), polymyositis, or autoimmune hemolytic anemia. By several criteria the antilysosome CF and precipitin reactions of SLE sera cound not be attributed to antibody to DNA, RNA, or other intracellular organelles. The lysosomal component reactive with SLE sera in CF assays was sedimentable at high speed and is presumably membrane associated. The CF activity of two representative SLE sera was associated with IgG globulins by Sephadex filtration. A search for lysosomal antigen in SLE and related disorders was also made. By employing rabbit antiserum to human lysosomes in immunodiffusion, a soluble lysosomal component, apparently distinct from the sedimentable (membrane-associated) antigen described above, was identified in serum, synovial fluid, or pleural fluid from patients with SLE, RA, ankylosing spondylitis, and leukemoid reaction. An antigenically identical soluble component reactive with the rabbit antiserum could be released in vitro from intact lysosomes by repeated freeze-thaw cycles..

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Introduction

Autoimmune hemolytic anemia in children younger than 2 years of age is usually characterized by a severe course, with a mortality rate of approximately 10%. The prolonged immunosuppression following specific treatment may be associated with a high risk of developing severe infections. Recently, the use of monoclonal antibodies (rituximab) has allowed sustained remissions to be obtained in the majority of pediatric patients with refractory autoimmune hemolytic anemia.

Case presentation

We describe the case of an 8-month-old Caucasian girl affected by a severe form of autoimmune hemolytic anemia, which required continuous steroid treatment for 16 months. Thereafter, she received 4 weekly doses of rituximab (375 mg/m2/dose) associated with steroid therapy, which was then tapered over the subsequent 2 weeks. One month after the last dose of rrituximab, she presented with recurrence of severe hemolysis and received two more doses of rrituximab. The patient remained in clinical remission for 7 months, before presenting with a further relapse. An alternative heavy immunosuppressive therapy was administered combining cyclophosphamide 10 mg/kg/day for 10 days with methylprednisolone 40 mg/kg/day for 5 days, which was then tapered down over 3 weeks. While still on steroid therapy, the patient developed an interstitial pneumonia with Acute Respiratory Distress Syndrome, which required immediate admission to the intensive care unit where extracorporeal membrane oxygenation therapy was administered continuously for 37 days. At 16-month follow-up, the patient is alive and in good clinical condition, with no organ dysfunction, free from any immunosuppressive treatment and with a normal Hb level.

Conclusions

This case shows that aggressive combined immunosuppressive therapy may lead to a sustained complete remission in children with refractory autoimmune hemolytic anemia. However, the severe life-threatening complication presented by our patient indicates that strict clinical monitoring must be vigilantly performed, that antimicrobial prophylaxis should always be considered and that experienced medical and nursing staff must be available, to deliver highly specialized supportive salvage therapies, if necessary, during intensive care monitoring.

We report a case of a 51-year-old woman with Evans syndrome (autoimmune hemolytic anemia and primary immune thrombocytopenia) and hypothyroidism. She was previously diagnosed with Hashimoto's thyroiditis in 1994 (age, 35) and autoimmune hemolytic anemia (AIHA) 3 years ago. She was treated with oral prednisolone. After a period, in which the anemia waxed and waned, there was an abrupt development of thrombocytopenia (nadir 15×109/L) that coincided with the tapering off of prednisolone after 3 years of administration. Because her thrombocytopenia was refractory to prednisolone, we administered rituximab (375 mg/m2 weekly) for 4 weeks. Two weeks after the completion of the rituximab treatment, her platelet count was up to 92×109/L. No intermittent peaking of thyroid stimulating hormone occurred after rituximab treatment was initiated. Evans syndrome and autoimmune thyroiditis might share common pathophysiological mechanisms. This notion supports the use of rituximab in a patient suffering from these disorders.

Objective: To study the prevalence of IgA antiphospholipid antibodies, particularly anticardiolipin antibodies (aCL) and anti-ß2-glycoprotein I (aß2GPI), in a cohort of patients with pregnancy morbidity.

Patients and methods: Serum samples from four groups of patients were studied by an in house enzyme linked immunosorbent assay (ELISA). Group I: 28 patients with primary antiphospholipid syndrome (PAPS) (median age 32.5 years, range 25–34). Twelve patients had a history of thrombosis. All were positive for IgG/M aCL or lupus anticoagulant (LA), or both. Group II: 28 patients with unexplained pregnancy morbidity (median age 35 years, range 23–48). Seven had history of thrombosis. Nine patients were positive for IgG/M aCL. None from this group fulfilled Sapporo criteria for APS. Group III: 28 patients with systemic lupus erythematosus (SLE) (median age 34 years, range 25–52). Eleven had a history of thrombosis. Twenty one patients had IgG/M aCL and/or LA, but only 19 fulfilled Sapporo criteria for APS.

Results: IgA aCL were found in 12, 6, and 14 patients from the groups with PAPS, unexplained pregnancy morbidity, and SLE, respectively. Most patients had these antibodies together with IgG/IgM aCL. Three patients from the group with unexplained pregnancy morbidity and two with SLE had IgA aCL alone. IgA aß2GPI was present in one patient from each group. All IgA aß2GPI were present together with IgG and/or IgM aß2GPI.

Conclusions: The prevalence of IgA aCL is high in patients with pregnancy morbidity, although IgA aCL are usually present together with IgG and/or IgM aCL. IgA aß2GPI are not useful in identifying additional women with APS and pregnancy morbidity.