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1.  Anti-C1q Antibodies as a Follow-Up Marker in SLE Patients 
PLoS ONE  2015;10(4):e0123572.
In cross-sectional studies autoantibodies against complement C1q (anti-C1q) were found to be highly associated with active lupus nephritis. The aim of this retrospective study was to determine the value of anti-C1q as follow-up marker of disease activity and renal involvement in patients with systemic lupus erythematosus (SLE). Fifty-two patients with SLE and a minimum of three anti-C1q measurements during follow-up were analyzed. Anti-C1q levels correlated with global disease activity scores. In subgroup analyses, patients without renal involvement did not show a significant correlation between anti-C1q levels and disease activity. In contrast, in patients with renal involvement, anti-C1q levels correlated well with global disease activity. In addition, a positive correlation with the urine protein-to-creatinine ratio and anti-dsDNA antibody levels as well as a negative correlation with complement levels was observed. Anti-C1q antibodies were found to strongly correlate with parameters of SLE disease activity during follow-up, in particular with regard to renal involvement.
PMCID: PMC4400137  PMID: 25881125
2.  Association between Low Levels of Mannan-Binding Lectin and Markers of Autoimmune Thyroid Disease in Pregnancy 
PLoS ONE  2013;8(12):e81755.
Functional deficiency of mannan-binding lectin (MBL) has been associated with adverse pregnancy outcome. Adverse events during pregnancy have also been described in women with autoimmune thyroid diseases (AITD), and thyroid hormones have been shown to influence serum levels of MBL. Therefore, the aim of this study was to analyse the impact of MBL-deficiency on the outcome of pregnancy in relation to the presence of AITD. Almost one year after delivery, we assessed serum MBL levels and MBL2-genotypes in 212 women positively screened for AITD in pregnancy. In 103 of these women, we could also measure MBL levels in frozen serum samples from the 9-12th gestational week, obtaining 96 pairs of MBL values (pregnancy vs. follow-up). As controls, 80 sera of pregnant women screened negatively for AITD were used. MBL2-genotyping was performed using multiplex PCR. Women with thyroid dysfunction and/or thyroid peroxidase antibodies (TPOAb) had lower MBL levels during pregnancy than controls, (3275 vs. 5000 ng/ml, p<0.05). The lowest levels were found in women with elevated thyroid-stimulating hormone (TSH) levels in the absence of TPOAb (2207 ng/ml; p<0.01 as compared to controls). MBL2 genotype distribution did not differ between subgroups. At a median follow-up period of 17 months (range: 3–78 months) after delivery, median MBL level had decreased further to 1923 ng/ml (p<0.0001) without significant changes in TSH. In an explorative survey, functional MBL-deficiency was neither linked to a history of spontaneous abortion, nor other obstetric complications, severe infections throughout life/pregnancy or antibiotics use in pregnancy. In conclusion, hypothyroidism during pregnancy is associated with decreased MBL levels, and the levels decreased further after delivery.
PMCID: PMC3858249  PMID: 24339961
3.  Impact of Mannose-Binding Lectin Deficiency on Radiocontrast-Induced Renal Dysfunction 
BioMed Research International  2013;2013:962695.
Contrast-induced nephropathy (CIN) is the third leading cause of acute renal failure in hospitalized patients. Endothelial dysfunction, renal medullary ischemia, and tubular toxicity are regarded as the most important factors in the pathogenesis of CIN. Mannose-binding lectin (MBL), a pattern recognition protein of the lectin pathway of complement, has been found to aggravate and mediate tissue damage during experimental renal ischemia/reperfusion (I/R) injury which was alleviated by inhibition with C1 inhibitor, a potent MBL, and lectin pathway inhibitor. In this paper, we highlight the potential role of MBL in the pathogenesis of human CIN. In experimental I/R models, MBL was previously found to induce tubular cell death independent of the complement system. In addition, after binding to vascular endothelial cells, MBL and its associated serine proteases were able to trigger a proinflammatory reaction and contribute to endothelial dysfunction. In humans, urinary MBL was increased after administration of contrast media and in individuals with CIN. Moreover, individuals with normal/high MBL levels were at increased risk to develop radiocontrast-induced renal dysfunction. Hence, MBL and the lectin pathway seem to be a promising target given that a licensed, powerful, human recombinant inhibitor exits to be added to the scarce armamentarium currently available for prophylaxis of CIN.
PMCID: PMC3872394  PMID: 24386641
4.  Three cases of primary small vessel vasculitis of the skeletal muscle–an own entity 
BMJ Case Reports  2011;2011:bcr0820114631.
Whereas systemic vasculitis is the most common form of vasculitis, vasculitis restricted to a single organ system is rare. Primary vasculitis restricted to striated skeletal muscle has been described in few case reports for polyarteritis nodosa and leucocytoclastic vasculitis, but not for small vessel vasculitis, type microscopic polyangiitis. The authors describe three patients with primary small vessel vasculitis of the skeletal muscle without evidence of other major organ involvement. All three patients presented with myalgias and highly elevated acute phase reactants while muscle weakness and elevated creatine kinase levels were not consistently present. Diagnoses were established by muscle biopsy and extensive search for potential causes of secondary vasculitis. Complete remission could be accomplished by steroids alone in only one case, while additional immunosuppressants were needed in the other two cases. Primary small vessel vasculitis of the skeletal muscle should be considered in patients presenting with myalgia and signs of systemic inflammation in the absence of other organ manifestations. Once diagnosed, aggressive systemic immunosuppression is appropriate.
PMCID: PMC3214212  PMID: 22674106
5.  Critical incidents in a tertiary care clinic for internal medicine 
BMC Research Notes  2013;6:276.
Reducing medical errors has become an international concern. Population-based studies consistently demonstrate inacceptable high rates of medical injury and preventable deaths. Thus, electronic critical incident reporting systems are now increasingly used in hospitals, predominantly in anesthesia. However, studies systematically analyzing critical incidents are scarce. Our aim was to describe content and causes of critical incidents in our Clinic for Internal Medicine.
We retrospectively analyzed all critical incidents reported during a 54-months period. Between implementation and analysis, 456 incidents were reported anonymously in the commercially available platform-independent, web-based critical incident reporting system. All incidents were analyzed according to the reporting profession, time point during hospitalization process, content and potential causes.
Most incidents occurred on medical wards (80%). The most frequent type of incidents was medication errors (62%). These incidents primarily occurred when prescribing and/or administering drugs (30% and 29% of medication errors respectively). So-called, human errors’, i.e. occurring without apparent external factor, were the most frequently indicated cause of critical incidents (56%) followed by insufficient communication (26%). These problems primarily occurred between different groups of health care professionals and between different departments. The described types and reasons of critical incidents remained stable during the observation period.
The findings of our analysis of the character and type of critical incidents occurring in a tertiary care clinic for internal medicine reported in an anonymous, voluntary, electronic reporting system suggest that strategies to improve communication and medication delivery are most promising to avoid critical incidents.
PMCID: PMC3729431  PMID: 23866793
Critical incidents; CIRS; Communication; Medication
6.  Low Levels of Mannan-Binding Lectin or Ficolins Are Not Associated with an Increased Risk of Cytomegalovirus Disease in HIV-Infected Patients 
PLoS ONE  2013;8(1):e51983.
In HIV-infected patients, prediction of Cytomegalovirus (CMV) disease remains difficult. A protective role of mannan-binding lectin (MBL) and ficolins against CMV disease has been reported after transplantation, but the impact in HIV-infected patients is unclear.
In a case-control study nested within the Swiss HIV Cohort Study, we investigated associations between plasma levels of MBL/ficolins and CMV disease. We compared HIV-infected patients with CMV disease (cases) to CMV-seropositive patients without CMV disease (controls) matched for CD4 T-cells, sampling time, and use of combination antiretroviral therapy. MBL and M-ficolin, L-ficolin, and H-ficolin were quantified using ELISA.
We analysed 105 cases and 105 matched controls. CMV disease was neither associated with MBL (odds ratio [OR] 1.03 per log10 ng/mL increase (95% CI 0.73–1.45)) nor with ficolins (OR per log10 ng/mL increase 0.66 (95% CI 0.28–1.52), 2.34 (95% CI 0.44–12.36), and 0.89 (95% CI 0.26–3.03) for M-ficolin, L-ficolin, and H-ficolin, respectively). We found no evidence of a greater association between MBL and CMV disease in patients with low CD4 counts; however in the multivariable analysis, CMV disease was more likely in patients with an increased HIV RNA (OR 1.53 per log10 copies/mL; 95% CI 1.08–2.16), or a shorter duration of HIV-infection (OR 0.91 per year; 95% CI 0.84–0.98).
CMV disease is not associated with low levels of MBL/ficolins, suggesting a lack of a protective role in HIV-infected patients.
PMCID: PMC3537714  PMID: 23308103
7.  Impact of mannose-binding lectin deficiency on radiocontrast-induced renal dysfunction: a post-hoc analysis of a multicenter randomized controlled trial 
BMC Nephrology  2012;13:99.
Local renal ischemia is regarded as an important factor in the development of contrast-induced nephropathy (CIN). Mannose-binding lectin (MBL) is involved in the tissue damage during experimental ischemia/reperfusion injury of the kidneys. The aim of the present study was to investigate the association of MBL deficiency with radiocontrast-induced renal dysfunction in a large prospective cohort.
246 patients with advanced non–dialysis-dependent renal dysfunction who underwent radiographic contrast procedures were included in the study. Baseline serum MBL levels were analyzed according to the occurrence of a creatinine-based (increase of ≥0.5 mg/dL or ≥25% within 48 hours) or cystatin C-based (increase of ≥10% within 24 hours) CIN.
The incidence of creatinine-based and cystatin C-based CIN was 6.5% and 24%, respectively. MBL levels were not associated with the occurrence of creatinine-based CIN. However, patients that experienced a cystatin C increase of ≥10% showed significantly higher MBL levels than patients with a rise of <10% (median 2885 (IQR 1193–4471) vs. 1997 (IQR 439–3504)ng/mL, p = 0.01). In logistic regression analysis MBL deficiency (MBL levels≤500 ng/ml) was identified as an inverse predictor of a cystatin C increase ≥10% (OR 0.34, 95% CI 0.15-0.8, p = 0.01).
MBL deficiency was associated with a reduced radiocontrast-induced renal dysfunction as reflected by the course of cystatin C. Our findings support a possible role of MBL in the pathogenesis of CIN.
PMCID: PMC3471006  PMID: 22938690
Complement; Mannose-binding lectin; Contrast-induced nephropathy; Ischemia/reperfusion injury; Acute kidney injury
8.  A Trial of Complement Inhibition in a Patient with Cryoglobulin-Induced Glomerulonephritis 
Cryoglobulinemia induces an immune complex-mediated glomerulonephritis that is characterized by the presence of large immune deposits, including complement C3 and C5b-9, marked macrophage influx and mesangial cell proliferation. The precise role of complement in cryoglobulin-induced glomerulonephritis in humans remains unclear, whereas in mice there has been evidence that complement activation might be a central factor favoring glomerular inflammation, particularly by the recruitment of neutrophils. We report on an exceptional case of cryoglobulin-induced glomerulonephritis in a patient with mixed essential cryoglobulinemia type II. The clinical features included relapsing proteinuria and renal function impairment that were controlled by plasmapheresis. Complement was low in plasma and two renal biopsies at 1-year interval showed prominent immunoglobulin and complement deposits, with unusual high numbers of neutrophils. In a 1-patient clinical trial, we tested whether the monoclonal anti-C5 antibody eculizumab would be sufficient to control renal function at the time of a relapse. Although during the initial weeks renal function was stabilized, slow increase in creatinine could not be controlled by this treatment, so that plasmapheresis was reinstituted. This result suggests that despite evidence for a role of complement in enhancing renal damage in this patient, other inflammatory processes dominated.
PMCID: PMC3482070  PMID: 23197954
Cryoglobulinemia; Glomerulonephritis; Complement inhibition
9.  Mannose-Binding Lectin Deficiency Is Associated With Smaller Infarction Size and Favorable Outcome in Ischemic Stroke Patients 
PLoS ONE  2011;6(6):e21338.
The Mannose-binding lectin (MBL) pathway of complement plays a pivotal role in the pathogenesis of ischemia/reperfusion (I/R) injury after experimental ischemic stroke. As comparable data in human ischemic stroke are limited, we investigated in more detail the association of MBL deficiency with infarction volume and functional outcome in a large cohort of patients receiving intravenous thrombolysis or conservative treatment.
Methodology/Principal Findings
In a post hoc analysis of a prospective cohort study, admission MBL concentrations were determined in 353 consecutive patients with an acute ischemic stroke of whom 287 and 66 patients received conservative and thrombolytic treatment, respectively. Stroke severity, infarction volume, and functional outcome were studied in relation to MBL concentrations at presentation to the emergency department. MBL levels on admission were not influenced by the time from symptom onset to presentation (p = 0.53). In the conservative treatment group patients with mild strokes at presentation, small infarction volumes or favorable outcomes after three months demonstrated 1.5 to 2.6-fold lower median MBL levels (p = 0.025, p = 0.0027 and p = 0.046, respectively) compared to patients with more severe strokes. Moreover, MBL deficient patients (<100 ng/ml) were subject to a considerably decreased risk of an unfavorable outcome three months after ischemic stroke (adjusted odds ratio 0.38, p<0.05) and showed smaller lesion volumes (mean size 0.6 vs. 18.4 ml, p = 0.0025). In contrast, no association of MBL concentration with infarction volume or functional outcome was found in the thrombolysis group. However, the small sample size limits the significance of this observation.
MBL deficiency is associated with smaller cerebral infarcts and favorable outcome in patients receiving conservative treatment. Our data suggest an important role of the lectin pathway in the pathophysiology of cerebral I/R injury and might pave the way for new therapeutic interventions.
PMCID: PMC3119675  PMID: 21712986

Results 1-9 (9)