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

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

Skewed distribution of IgG Fc receptor IIa (CD32) polymorphism is associated with renal disease in systemic lupus erythematosus patients

Objective. Fc gamma receptors of class IIa (Fc gamma RIIa) occur in 2 allelic forms, with either a low (IIa-R131) or a high (IIa-H131) affinity for complexed IgG2 and IgG3. This polymorphism might have implications for the handling of immune complexes. Therefore, we determined the distribution of the Fc gamma RIIa allotypes in patients with systemic lupus erythematosus (SLE), with or without a history of lupus nephritis. Methods. We studied 95 unrelated white European patients with SLE, as defined by the American College of Rheumatology criteria, 50 of whom had a history of lupus nephritis, and 69 healthy white European control subjects. Fc gamma RIIa allotypes were determined by immunophenotyping of blood monocytes. Results. It was found that lupus nephritis was significantly associated with the ''low affinity'' Fc gamma RIIa R/R131 allotype and with the R131 allele, compared with healthy controls. No significant association was found upon comparison of groups with and without nephritis. Conclusion. SLE patients with a history of lupus nephritis have an abnormal distribution of Fc gamma RIIa allotypes. Fc gamma RIIa may well play a role in the pathogenesis of lupus nephritis, since IIa-R/R131 SLE patients seem to have a higher incidence of developing this complication

Relevance of Fcgamma receptor and interleukin-10 polymorphisms for meningococcal disease

The contribution of individual Fcgamma receptor (FcgammaR) subclasses to meningococcal phagocytosis was studied. In addition, functional FcgammaR polymorphisms were determined in 50 patients with meningococcal disease (MD), in 183 first-degree relatives of MD patients, and in 239 healthy control subjects, to study the association of FcgammaR genotypes with disease. Efficient internalization of opsonized Neisseria meningitidis serogroup B was mediated via multiple FcgammaR subclasses on phagocytes. Accordingly, a low-efficiency combination of FcgammaRIIa-R/R131, FcgammaRIIIa-F/F158, and FcgammaRIIIb-NA2/2 genotypes was increased significantly in relatives of patients with MD, compared with healthy control subjects (P <.05; odds ratio, 2.6; 95% confidence interval, 1.1-6.3). FcgammaRIIa and FcgammaRIIIa genotype distributions differed between patients with sepsis and those with meningitis. Combined genotypes of FcgammaRIIa and interleukin-10 -1082, which was previously reported as being associated with MD outcome, were distributed randomly in control subjects but not in relatives of patients with MD (P <.01). These data provide further evidence for the association of polymorphic genes on chromosome 1 and M

Analysis of the expression of stem cell and EMT related genes in different sub-populations from the PLCCLs.

<p>Detectable expression levels of the genes were found in all sorted sub-populations from the cell lines LC004 (<b>A</b>), LC006 (<b>B</b>) and LC021 (<b>C</b>). PCR reaction without template served as a negative control. The relative expression of target genes was related to the expression of <i>PGK1</i> and normalized to the unsorted control cells. X axis shows the target genes, Y axis shows the relative expression level (RQ). The error bars reflect the variation within the triplicates, <i>P</i><0.05. (B). The FACS sorted cell sub-populations derived from the cell line LC006 were cultured in the serum-free culture system for 1–2 weeks and revealed different cell morphology for different sorted sub-populations: (a) CD44highCD90+ cells; (b) CD44highCD90− cells; (c) CD44low/−CD90+ cells, and (d) CD44low/−CD90− cells. Photomicrograph magnification, ×200.</p