Lack of association of FcγRIIIb polymorphisms with systemic lupus erythematosus: a meta-analysis.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease. Fcγ receptor genes have been suggested to play an important role in the pathogenesis of SLE and lupus nephritis (LN). This study aims to assess the association between FcγRIIIb-NA1/NA2 polymorphism and the susceptibility to SLE and lupus nephritis. Relevant studies were identified from electronic databases. A meta-analysis was performed for heterogeneity test and pooled OR calculation. The overall OR of NA2/NA2 homozygous genotype and NA2 allele frequency showed no significant association with SLE and lupus nephritis. Similarly, the association between FcγRIIIb-NA1/NA2 polymorphism and SLE and lupus nephritis was not found in European and Asian population. Taken together, our results suggest that FcγRIIIb might not be a susceptibility gene for SLE and lupus nephritis.

A meta-analysis of the association of STAT4 polymorphism with systemic lupus erythematosus.

STAT4 has been newly identified as a susceptibility gene for systemic lupus erythematosus (SLE) in recent reports. To more precisely estimate the association between STAT4 polymorphism and SLE risk, a meta-analysis was performed. Studies on the association of STAT4 rs7574865 or rs7601754 with SLE were fully considered and carefully selected using three electronic databases (PubMed, Embase, and Web of Science). A total of 17 comparisons from 8 relevant studies involving 7,381 patients and 11,431 controls were included to analyze the association between STAT4 rs7574865 and SLE risk. The pooled OR for the minor T allele of STAT4 rs7574865 was 1.65 (95% CI 1.56-1.75, P < 0.001) in SLE. In a subgroup analysis by ethnicity, the degree of risk of STAT4 rs7574865 with SLE susceptibility was similar in populations of European or Asian origin, although significant differences in the minor T allele frequencies were observed in the two population controls. As for rs7601754, there were five comparisons from four relevant studies involving 2,498 patients and 4,825 controls in this meta-analysis. The pooled OR for the minor C allele of STAT4 rs7601754 was 0.67 (95% CI 0.59-0.75, P < 0.001) in SLE. Conversely, the major T allele of STAT4 rs7601754 might be a risk factor for SLE risk. In conclusion, our results do support STAT4 rs7574865 polymorphism as a susceptibility factor for SLE in populations of European and Asian origin. Our results also suggest that STAT4 rs7601754 polymorphism might be associated with SLE risk.

Gender and age influence on clinical and laboratory features in Chinese patients with systemic lupus erythematosus: 1,790 cases.

This study aims to review the cumulative clinical and laboratory data of 1,790 Chinese patients with systemic lupus erythematosus. Data were compared separately between male and female patients for each disease onset age groups and among three disease onset age groups in male and female patients. The ratio of female to male was 9.2:1, with differences among three age groups. There was no difference in mean age at onset between females and males. But diagnosis delay in male patients is shorter than in females. When compared with females, in adult-onset patients, males presented more frequently with serositis, pleuritis and discoid rash, but less frequently with malar rash, alopecia, oral ulcers, elevated erythrocyte sedimentation rate, anti-nuclear, anti-SSA and anti-SSB antibodies. In younger-onset group, males have less discoid rash. In older-onset group, males have less anti-SSA antibodies. In male patients, only anti-SSB antibodies were different in three age groups and negatively correlate to age. Among female patients, age had negative correlations with malar rash, discoid rash, photosensitivity, anti-dsDNA, anti-Sm, anti-SSB and anti-rRNP antibodies, but positive correlation with leucopenia. We conclude that women of childbearing age possess a distinct clinical and laboratory profile. In addition, differences in disease manifestations seem to be correlated with female sex hormones rather than age.

The expressions of Toll-like receptor 9 and T-bet in circulating B and T cells in newly diagnosed, untreated systemic lupus erythematosus and correlations with disease activity and laboratory data in a Chinese population.

Toll-like receptor 9 (TLR9) plays a controversial role in the pathogenesis of systemic lupus erythematosus (SLE). T-bet may be involved in the processes between the initiation of TLR9 activation and the antibodies' production. To clarify the paradox of TLR9, we investigated the intracellular expressions of TLR9 and T-bet in B and T cells in peripheral blood samples from 35 newly diagnosed, untreated patients with SLE and 16 healthy subjects by flow cytometry (FCM). And we collected the clinic laboratory data obtained from the same individual blood sample tested by FCM each time. And the correlations among the expression levels of the two proteins and SLE laboratory data were calculated. We found the percentages of B cells expressing TLR9 and T-bet and of T cells expressing TLR9 were significantly elevated in SLE patients when compared with healthy controls. There was a significantly negative relationship between the proportion of B cells expressing TLR9 and SLE Disease Activity Index (SLEDAI) score. The serum levels of anti-dsDNA antibody reversely correlated with the mean fluorescence intensity (MFI) of B cells co-expressing T-bet and TLR9. The serum levels of anti-C1q antibody significantly associated with the proportion of B cells expressing T-bet. Also, the serum levels of IgM and IgA antibodies both significantly correlated with TLR9 and T-bet expressions in T and B cells. According to the immunological pathway knowledge and the mutually verified associations, the following conclusions are made. Expressions of TLR9 and T-bet were increased in patients with SLE. TLR9 may have a role to play in protecting against lupus. And the increase of the co-expression of TLR9 and T-bet may be of benefit to the protective antibodies' production and pathogenic antibodies' decline, and could be regarded as a good sign for lupus demission and/or treatment.

Meta analysis on the association between FcgammaRIIa-R/H131 polymorphisms and systemic lupus erythematosus.

In order to study the association between FcgammaRIIa gene polymorphisms and the risk of systemic lupus erythematosus (SLE) and lupus nephritis, relevant studies were identified from electronic databases. A meta-analysis of relevant studies was performed for heterogeneity test and pooled OR calculation. When all groups were pooled, a significant association of FcgammaRIIa-R131 allele and increased SLE risk was found. But this association was not observed in lupus nephritis. In the subgroup analysis, a clear effect of R allele in SLE was shown in European and Asian subgroups. Similarly, RR homozygous genotype was found to be a risk factor of SLE and lupus nephritis. The association between RR genotype and SLE was shown in European and Asian descents. However, the association between RR genotype and lupus nephritis was not found in any ethnic subgroups. Taken together, our study suggests that the FcgammaRIIa-R/H131 polymorphism might contribute to the susceptibility to SLE and lupus nephritis.