Human leukocyte antigen-G (HLA-G) is a nonclassical class I major histocompatibility complex molecule which is induced at the course of inflammatory pathologies, and its expression has been suggested as a possible mechanism of tissue protection against autoimmune inflammatory responses, therefore acting as a mechanism of immune surveillance. We investigated the influence of the 14 bp polymorphism of the HLA-G gene on systemic lupus erythematosus (SLE) by analyzing 293 patients with SLE and 460 healthy controls. The patient's group was not in Hardy-Weinberg equilibrium, presenting an excess of heterozygotes (P = 0.014). The heterozygote group exhibited lower systemic lupus erythematosus disease activity indexes than the homozygous deletion group and the homozygous insertion group (mean value = 2.29 against 2.97 and 3.4, respectively, P = 0.035). Photosensitive patients showed a higher frequency of heterozygotes and an equivalent lower frequency of homozygotes for deletion; on the other hand, patients without arthritis presented a higher frequency of heterozygotes than the arthritis group and also a lower frequency of the del/del genotype. Overall, our results support the idea of a role of the HLA-G insertion/deletion polymorphism and therefore a role for the HLA-G molecule, on the pathology of SLE.

Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease that affects several organs and systems. Its etiology remains unknown, although it is probably multifactorial. The human leukocyte antigen G (HLA-G) is a nonclassic major histocompatibility complex I molecule characterized by restricted expression and low DNA polymorphism. HLA-G plays a role in immunosuppression through different mechanisms. In inflammatory diseases, it has been postulated that HLA-G expression may be a possible mechanism of tissue protection against exacerbated inflammatory response. On the 3' untranslated region (3' UTR) of the HLA-G gene, there is an insertion/deletion polymorphism of 14 bp (rs1704) that was shown to influence the mRNA stability. The influence of this polymorphism in disease susceptibility is controversial. Also in the 3' UTR there is a single nucleotide polymorphism C/G (rs1063320) on the position +3142, at a possible binding site for microRNAs (miRNAs) and having an influence on miRNA affinity. In this study, we analyzed the +3142C>G and the 14 bp polymorphisms in 195 SLE European-derived female patients. Our findings show a significant increase of the +3142G allele frequency among patients as compared with controls (0.58 vs 0.47, P = 0.011). Also, patients presented a higher frequency of the GG genotype (OR = 1.90, 95% CI: 1.08-3.42). Double heterozygotes for the two polymorphisms presented a milder mean systemic lupus erythematosus disease activity index (SLEDAI) than heterozygotes for only one of the variants or non-heterozygous individuals (1.56 vs 3.15 and 3.26, respectively, corrected P = 0.044). These results suggest the involvement of the HLA-G molecule on SLE susceptibility and outcome.

This LANSS version was found to be a reliable instrument for the evaluation of pain complaints due to a variety of causes. The profile of pain scores was similar to that observed in other countries.

Susceptibility to systemic lupus erythematosus (SLE) is associated with genetic, hormonal, immunological, and environmental factors. Many genes have been related with the appearance of SLE, including several loci that code different complement components and their receptors. Some genetic deficiencies of complement molecules are strongly associated with SLE, probably because these deficiencies could cause decreased clearance of apoptotic cell material. As a consequence of the apoptotic material accumulation, high levels of autoantigens can be presented inappropriately to the immune system in an inflammatory context, resulting in an imbalance on the mechanisms of immunological tolerance, immune system activation, and autoantibody production. Recent studies proposed a role to the mannose-binding lectin (MBL) in the SLE physiopathogenesis. This protein activates the complement system, and the presence of several polymorphisms at the promoter and coding regions of the MBL-2 gene determines alterations at the plasma levels of MBL. Some of these polymorphisms have been associated with SLE susceptibility, as well as with clinical and laboratory typical features of this disease, cardiovascular events, and infections. Besides, it has been described that the presence of anti-MBL autoantibodies in sera of SLE patients can influence MBL plasma levels and its functional activity.

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The mannose-binding lectin gene (MBL-2) has emerged as a candidate for systemic lupus erythematosus susceptibility, but studies in Brazilian population have not been conducted. To examine potential associations of mannose-binding lectin alleles G57E, G54D, IVSnt5, R52C and R52H with susceptibility to and clinical expression of systemic lupus erythematosus in southern Brazilian patients, we conducted a case-control study with 327 consecutive patients with diagnosis of systemic lupus erythematosus and 345 healthy controls. Genotyping was performed by restriction fragment length polymorphism-polymerase chain reaction assay. A statistically significant difference in the frequencies of allele R52C was observed in European-derived systemic lupus erythematosus patients when compared with controls (9.6% vs. 3.3%, p < 0.001, odds ratio: 3.15, 95% confidence interval: 1.76-5.62, p < 0.05). The frequencies of alleles G54D and G57E were not different between European-derived systemic lupus erythematosus patients and controls. There were no differences between clinical and laboratory features in systemic lupus erythematosus patients according to the presence or absence of mannose-binding lectin allelic variants. These results support an increased risk of systemic lupus erythematosus in European-derived individuals carrying allele R52C. Patients carrying this allele have an approximately three-fold higher odds ratio of developing systemic lupus erythematosus when compared with controls. Our data do not support associations between the mannose-binding lectin allelic variants studied and clinical expression of systemic lupus erythematosus.

Recebido para publicação em 16/12/96 Revista da Sociedade Brasileira de Medicina Tropical 30(5):355-357, set-out, 1997.