HLA Markers for Poor Prognosis in Systemic Sclerosis Brazilian Patients

Abstract

Objectives. The aim of this study was to evaluate human leukocyte antigen (HLA) involvement in the disease expression and poor prognostic clinical features (pulmonary fibrosis and pulmonary arterial hypertension) in patients diagnosed with systemic sclerosis (SSc) in a multiethnic population. Methods. SSc patients followed up between 2008 and 2011 were included, and clinical data were obtained through records review. Molecular HLA typing was performed (polymerase chain reaction amplification technique using specific primer sequences). The statistical analysis involved Fisher's exact test and Pearson's corrected chi-square test. P values ≤ 0.05 were considered significant. The delta method was used to estimate the variance of the prevalence ratio (PR). Results. A total of 141 patients (120 women and 21 men) with SSc were studied, including 33.3% with diffuse cutaneous SSc (dcSSc), 62.4% with limited cutaneous SSc (lcSSc), and 4.3% with sine scleroderma. Pulmonary fibrosis was present in 61 patients (43.3%), and the HLA-A∗30 and DQB1∗04 alleles were related to susceptibility. In contrast, the HLA-DRB1∗01 and DQB1∗05 alleles were protective. Pulmonary arterial hypertension was diagnosed in 19 patients (13.5%) and was associated with HLA-B∗35 and C∗04; in contrast, C∗03 seemed to be protective. Conclusions. Our current study documents the association of some classes I and II HLA alleles with the most severe clinical manifestations in a multiethnic case series. Our findings differed slightly from the previous data in other populations.

KIR/HLA Gene Profile Implication in Systemic Sclerosis Patients from Mexico

“…In a previous study in Mexican patients, the genes -C ∗ 12:03/-B18:01 and -B ∗ 08:01 were reported as a genetic risk to SSc, whereas -C ∗ 07:02 , -C ∗ 07:02+/-B ∗ 39:05 , and -B ∗ 39:06 were reported with reduced risk to dcSSc development [25]. In Brazilian patients, alleles of HLA-I have been associated not only with SSc development ( -A ∗ 30 , -A ∗ 32 , -B ∗ 57 and -Cw14 ) but also with medical complications, such as pulmonary fibrosis ( -Cw ∗ 0602 ) and pulmonary arterial hypertension ( -C ∗ 04 ) [44]. Thus, the presence of HLA class I genes may have a role in SSc susceptibility and development.…”

Pathogenesis of Systemic Sclerosis

“…HLA-A*30 and - DQB1*04 alleles were found to relate to SSc susceptibility in a subset of Brazilian patients ( 16 ). In patients who had PAH, HLA-B*35 , and C*04 were associated as risk genes for this complication, while C*03 was protective ( 16 ). HLA-DRB1*15:02 and DRB5*01:02 are associated with ATA positivity in SSc Thai patients.…”

Contribution of HLA and KIR Alleles to Systemic Sclerosis Susceptibility and Immunological and Clinical Disease Subtypes

“…Although less frequently reported, HLA class I associations with SSc suggest an additional role for CD8 + T cell mediated autoimmunity in disease. Early studies show enrichment of the HLA-A*09 subgroup allele HLA-A*24 in dcSSc, and HLA-A*30 and HLA-A*32 risk associations have also been reported in Caucasian and Brazilian populations, the former associated with risk of pulmonary hypertension and pulmonary fibrosis in SSc patients ( Gladman et al, 2005 ; Del Rio et al, 2013 ). A recent intensive analysis of 9,095 SSc patients identified a significant disease risk association with HLA-B*08:01 , independent of those observed with HLA Class II alleles ( Acosta-Herrera et al, 2021 ).…”