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. 2002 Sep;61(9):786–792. doi: 10.1136/ard.61.9.786

Fcγ receptor IIa, IIIa, and IIIb polymorphisms in German patients with systemic lupus erythematosus: association with clinical symptoms

K Manger, R Repp, M Jansen, M Geisselbrecht, R Wassmuth, N Westerdaal, A Pfahlberg, B Manger, J Kalden, J G J van de Winkel
PMCID: PMC1754233  PMID: 12176802

Abstract

Background: Receptors for IgG play an important part in immune complex clearance. Several studies have identified polymorphisms of receptors for the Fc fragment of IgG (FcγR) as genetic factors influencing susceptibility to disease or disease course of systemic lupus erythematosus (SLE).

Objective: To examine these possibilities by evaluating a panel of clinical parameters in a cohort of 140 German patients with SLE for correlations with the FcγRIIa, IIIa, and IIIb polymorphisms in an explorative study.

Methods: 140 German patients with SLE according to American College of Rheumatology (ACR) criteria and 187 German controls were genotyped for the FcγRIIa, IIIa, and IIIb polymorphisms. Associations between FcγR genotypes, combined genotypes and clinical as well as laboratory features were analysed.

Results: No significant skewing of any of the three FcγR polymorphisms was seen in the German SLE cohort studied. Various clinical and serological parameters were found more frequently and at younger age in homozygous patients with the genotypes IIA-R/R131 or IIIA-F/F158 than in patients with IIA-H/H131 or IIIA-V/V158. These effects were even more pronounced in patients with the low binding combined phenotypes of the FcγRIIa, IIIa (double negative phenotypes) and FcγRIIa, IIIa, and IIIb (triple negative phenotypes). In patients with the double negative IIA and IIIA genotypes significantly higher frequencies of nephritis (63% v 33%) and proteinuria according to ACR criteria (58% v 11%), anaemia (84% v 55%), and anticardiolipin antibodies (63% v 22%) were found than in patients with the double positive genotypes. Patients with the IIA-R/R131 genotype and the double negative homozygous genotype had an earlier incidence of clinical symptoms, haematological and immunological abnormalities. Accordingly, SLE is diagnosed earlier in these patients, the difference reaching statistical significance only in the double negative v the double positive genotype (26.3 v 39.5 years) and the IIIA-F/F158 genotype v the rest (26.7 v 32.0 years). Most relevant is the fact that a higher median disease activity (ECLAM score) was demonstrated, both in the IIA-R/R131 homozygous (3.3 v 2.7) and the double negative (3.4 v 2.3) patients, reaching statistical significance in the first group.

Conclusion: The results of this explorative study support the view that the FcγRIIa/IIIa and IIIb polymorphisms constitute factors influencing clinical manifestations and the disease course of SLE but do not represent genetic risk factors for the occurrence of SLE. Higher frequencies of clinical symptoms, haematological and immunological abnormalities as well as an earlier onset of clinical symptoms, haematological and immunological markers of active disease were found in patients with the IIA-R/R131 genotype and the double negative and triple negative genotypes.

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Figure 1 .

Figure 1

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Overrepresentation of the homozygous low binding genotypes FcγRIIA-R/R131, FcγRIIIA-F/F158, and FcγRIIA/IIIA-R/R131, F/F158 (double negative) in patients with SLE and nephritis. Differences are not significant. n=57 for patients with nephritis, n=140 for all patients, n=83 for patients without nephritis.

Figure 2 .

Figure 2

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Prevalence of nephritis, proteinuria, and anaemia in patients with SLE with the homozygous genotypes FcγRIIA/IIIA-R/R131, F/F158 (double negative), FcγRIIA-R/R131, FcγRIIA/IIIA-H/H131, V/V158 (double positive), and FcγRIIA-H/H131. Statistical differences for the frequency of each symptom were calculated with a χ2 test. The differences between columns 1 and 3 and columns 2 and 4 were significant for nephritis, proteinuria, and anaemia (p<0.05).

Figure 3 .

Figure 3

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Kaplan Meier analysis of onset of (A) nephritis and (B) proteinuria according to the double negative (dashed line) versus double positive (solid line) homozygous FcγRIIA/IIIA genotypes. The difference between haplotypes was estimated with a log rank test; the p value indicates the level of significance.

Selected References

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