MBL2 gene variants coding for mannose-binding lectin deficiency are associated with increased risk of nephritis in Danish patients with systemic lupus erythematosus.
OBJECTIVE
Autoimmunity may in part result from deficiencies in the processing of apoptotic debris. As mannose-binding lectin (MBL) is involved in such processes, we hypothesized that the variants in the MBL2 gene resulting in MBL deficiency confer an increased risk of nephritis in systemic lupus erythematosus (SLE).


METHODS
A total of 171 SLE patients attending a Danish tertiary rheumatology referral center were included. Common variant alleles in exon 1 of the MBL2 gene (R52C, rs5030737; G54D, rs1800450; G57E, rs1800451) were genotyped. The normal allele and variant alleles are termed A and O, respectively. The follow-up period was defined as the time from fulfillment of the ACR 1987 classification criteria for SLE until the occurrence of an event (nephritis, end-stage renal disease (ESRD), or death) or end of follow-up. Cox regression analyses were controlled for gender, age and race.


RESULTS
During a median follow-up of 5.7 years, nephritis developed in 94 patients, and ESRD developed in 16 of these patients. Twenty-seven patients died. The distribution of the MBL2 genotypes A/A, A/O and O/O was 58%, 35% and 7.0%, respectively. Compared to the rest, O/O patients had 2.6 times (95% CI: 1.2-5.5) higher risk of developing nephritis, and their risk of death after 10 years was 6.0 times increased (95% CI: 1.0-36). MBL serum levels below 100 ng/ml were associated with a 2.0 (95% CI: 1.2-3.4; p = 0.007) increased risk of developing nephritis. ESRD and histological class of nephritis were not associated with MBL deficiency.


CONCLUSIONS
Genetically determined MBL deficiency was associated with development of nephritis in SLE patients, but not with histological class of nephritis or ESRD.
Department of Rheumatology.
N
N
Tanha
Department of Rheumatology Laboratory of Molecular Medicine, Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Denmark.
L
L
Troelsen
Department of Rheumatology.
M-L
ML
From Hermansen
Department of Rheumatology.
L
L
Kjær
Department of Rheumatology.
M
M
Faurschou
Laboratory of Molecular Medicine, Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Denmark.
P
P
Garred
Department of Rheumatology sj@dadlnet.dk.
S
S
Jacobsen
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D002648:Child; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000150:complications* / Q000235:genetics; D008181:Lupus Nephritis / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D037601:Mannose-Binding Lectin / Q000172:deficiency* / Q000235:genetics; D008661:Metabolism, Inborn Errors / Q000235:genetics*; D008875:Middle Aged; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012307:Risk Factors; D055815:Young Adult
C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin
Systemic lupus erythematosus; end-stage renal disease; lupus nephritis; mannose-binding lectin; mortality; pathogenesis