Collectins are a family of well-conserved C-type lectins that contain a collagen-like domain and a carbohydrate recognition domain. Collectins interact with complement proteins to effect opsonization of pathogens. They are traditionally classified into three groups – mannose binding lectin (MBL), surfactant protein A (SFTPA), and surfactant protein D (SFTPD).
MBL is the prototypic C-type lectin opsonin and functions by interacting with complement components during the innate immune response. It assists in clearing apoptotic debris that could trigger an anti-nuclear autoimmune response. Genetic variants of MBL, including a promoter SNP and a SNP in exon 1, are associated with SLE risk [29
], as are variants of MBL2, a molecule that modifies MBL expression level. Both low MBL levels [30
] and presence of anti-MBL antibodies [31
] are correlated with SLE providing additional evidence for the involvement of MBL in disease.
SFTPA, encoded by a cluster of genes on Chromosome 10q22, targets pathogens and apoptotic debris for phagocytosis by alveolar macrophages. SFTPD, which has a collagen domain structurally homologous with C1q, can enhance phagocytosis by alveolar macrophages via FcR and complement receptor engagement. The roles of surfactants as candidate genes for SLE, including pulmonary manifestations [32
], is unexplored.
COLEC11 (CL-K1), another collectin family member, recognizes sugars on bacterial surfaces, while COLEC12 (CL-P1) functions as a scavenger receptor that binds microorganisms and oxygen radical damaged phospholipids to speed recognition by phagocytes. Not all collectins function directly in opsonization though since some, such as COLEC10, are only found in the cytoplasm.
Ficolins, another family of molecules with opsonic properties, include a collagen-like domain that provides them with homology to collectins. Ficolin 2 can bind DNA leading to increased attachment and engulfment of necrotic cells by macrophages. Ficolin 3 has been observed at increased levels in the serum of SLE patients [33
], which is consistent with a function in reducing auto-inflammation by clearing apoptotic debris.
Pentraxins are innate immune molecules that recognize microbial, nuclear, and apoptotic antigens, initiate complement activation, and bind directly to phagocyte FcRs. One pentraxin family member, C-reactive protein (CRP), is an acute phase molecule known to mediate phagocytic responses by binding microorganisms and nuclear materials such as histones and chromatin. Impairment of nuclear antigen clearance by CRP may be one way it influences the pathogenesis of SLE since lowered serum levels of CRP have been related to disease presence and clinical activity [34
]. Genetic variation linked to reduced CRP expression has associated with SLE in a British study [35
], and a promoter SNP, rs3093061, is associated in African-Americans and Caucasians [36
variants can also influence clinical manifestations in SLE such as development of nephritis and vascular disease.
Amyloid P component of serum (APCS) [also called serum amyloid P], also functions as an opsonin for microorganisms. Its gene is located near CRP
on Chromosome 1 within a lupus susceptibility region [35
]. Like CRP, APCS binds chromatin and signals through FcRs, thereby, potentially playing a role in a nuclear-based autoimmune condition such as SLE. While elevated levels of APCS have not been reported in SLE patients, there is an inverse relationship between the presence of anti-dsDNA antibodies, a common serological marker for SLE, and APCS DNA complexes. This is consistent with the decreased amount of APCS DNA complexes measured in SLE patients [37
]. Serum levels of anti-APCS antibodies are, however, raised in SLE patients and relate to disease activity, further suggesting a pathogenic role for this opsonin [38
Pentraxin 3 (PTX3) binds to apoptotic cells to influence phagocytosis; it sequesters pathogenic debris from antigen-presenting cells to limit autoimmune reactions in inflamed tissues. However, unlike CRP, a correlation between levels of PTX3 SLE risk has not yet been observed [39