Mannose-binding protein gene polymorphism in systemic lupus erythematosus

Abstract

Objective. To determine whether an allelic form of mannose-binding protein (MBP) incapable of activating complement is associated with susceptibility to systemic lupus erythematosus (SLE).Methods. MBP allele frequencies were determined by amplification refractory mutation systempolymerase chain reaction in 102 white SLE patients and 136 controls.Results. The MBP allele that is unable to activate complement was present in 42 SLE patients ( Conclusion. Our results suggest that this allele of the MBP gene represents a minor risk factor for SLE.Both genetic and environmental factors are important in the development of systemic lupus erythematosus (SLE). This is indicated by a disease concordance of -24% in monozygotic twins (1) as compared with only 3% in dizygotic twins (2). It is likely that the genetic component of SLE susceptibility is oligogenic, and it is known that HLA-encoded genes play an important role. Previous studies have shown that HLA-DQ alleles are important risk factors

Mannose-Binding Lectin-Deficient Mice Display Defective Apoptotic Cell Clearance but No Autoimmune Phenotype

“…Furthermore, SPD null animals have defective in vivo clearance of apoptotic cells in the lung (14). These observations suggest that MBL could also have a role in apoptotic cell clearance in vivo and, along with the reports of increased risk of autoimmunity in MBL low individuals (6,7), have raised the question of whether lack of MBL might result in autoimmunity as is observed with C1q deficiency (15). To study the role of MBL in vivo, we have generated mice deficient in both genes encoding mouse MBL (MBLA and MBLC) (3), and here we report the role of MBL in autoimmunity.…”

“…Defects in the first component of complement are strongly associated with autoimmunity such that Ͼ95% of patients deficient in C1q develop a systemic autoimmune syndrome (5). In addition, MBL haplotypes that specify low levels of an aberrant form of MBL unable to activate complement are also reported to be associated with a low but increased risk of autoimmunity (6,7). Apoptotic cells have been shown to be a preferential source of many autoantigens (8) and failure to promptly remove dying cells has been implicated in the pathogenesis of systemic lupus erythematosus (5, 9, 10), a prototypic autoimmune disease.…”

The Genetics of Systemic Lupus Erythematosus

“…It also interacts with viral envelopes containing mannose protein, such as the immunodeficiency virus [58]. One particular allele of the MBP gene, which is unable to activate the classical pathway of the complement, has shown a moderate association with SLE in two different ethnic populations [59,60].…”

Mannose binding lectin (MBL) gene mutation is not a risk factor for systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in Japanese

“…In the study of 102 SLE patients in the UK, and 111 Chinese SLE patients in Hong Kong, there was a modest but statistically not significant increase in the frequency of G54D mutation (0.25 in SLE patients vs 0.19 in controls; odds ratio 1.5 and 0.17 in SLE patients vs 0.11 in controls; odds ratio 1.7). 10,12 In the 50 Spanish SLE patients, a significant increase in the G54D frequency (0.28 in SLE patients vs 0.16 in controls) has been reported. 11 However, the allele frequency of G54D mutation in our 95 SLE patients was 0.226 that was comparable to the frequency of 0.233 in controls.…”

“…Studies in the UK and Spanish populations, as well as in Hong Kong Chinese have suggested the association of MBL deficiency with systemic lupus erythematosus (SLE). [10][11][12] In the case of rheumatoid arthritis (RA), results are controversial. Presence 13 or absence 14,15 of association of MBL deficiency with RA have been reported.…”