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Association of serum TNF-?, IL-8 and free light chain with HLA-DR B alleles expression in pulmonary and extra-pulmonary sarcoidosis.

ABSTRACT: BACKGROUND:Sarcoidosis is a systemic disease of unknown etiology characterized histologically by the observation of non-caseating granulomas and several immunological abnormalities. Sarcoidosis is a multi-organ disorder which involves formation of granulomas in many tissues including the lungs (pulmonary) and others such as skin, bone, heart (extra pulmonary). Associations between human leukocyte antigens (HLA), the encoded cell surface receptor (HLA-DR) and sarcoidosis have been reported in several studies. Several HLA-DR alleles have been described as potential risk factors for sarcoidosis in distinct ethnic groups however evidence for a relationship between HLA-DR alleles and pulmonary and extra-pulmonary sarcoidosis (EPS) is still scarce. Although the etiology of the disease remains unclear, infectious and environmental factors have been postulated. Inflammatory cytokines and chemokines may play important roles in the pathogenesis of sarcoidosis and serum free light chain (FLC) numbers have been implicated in several immunologic disorders. PURPOSE OF THE STUDY:The aim of the present study was to investigate HLA associations with serum cytokines and FLC in Iranian patients with pulmonary (n = 86) and EPS (n = 46). RESULTS:We found that among the 16 HLA DRB alleles only *7 and *12 were different in sarcoidosis patients. The levels of TNF-? and IL-8 in pulmonary sarcoidosis patients were higher than in EPS (P < 0.05) whereas the levels of FLC subunits in EPS were higher than in pulmonary sarcoidosis. CONCLUSION:This data may suggests a link between HLA-DRB *12 and sarcoidosis in Iranian population.

SUBMITTER: Mortaz E

PROVIDER: S-EPMC4393873 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Association of serum TNF-α, IL-8 and free light chain with HLA-DR B alleles expression in pulmonary and extra-pulmonary sarcoidosis.

Mortaz Esmaeil E Sereshki Hale Abdoli HA Abedini Atefeh A Kiani Arda A Mirsaeidi Mehdi M Soroush Dina D Garssen Johan J Velayati Aliakbar A Redegeld Frank A FA Adcock Ian M IM

Journal of inflammation (London, England) 20150319

<h4>Background</h4>Sarcoidosis is a systemic disease of unknown etiology characterized histologically by the observation of non-caseating granulomas and several immunological abnormalities. Sarcoidosis is a multi-organ disorder which involves formation of granulomas in many tissues including the lungs (pulmonary) and others such as skin, bone, heart (extra pulmonary). Associations between human leukocyte antigens (HLA), the encoded cell surface receptor (HLA-DR) and sarcoidosis have been reporte ...[more]

PMID: 25866481

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Project description:BACKGROUND:Asthma afflicts 6% to 8% of the United States population, and severe asthma represents approximately 10% of asthmatic patients. Several epidemiologic studies in the United States and Europe have linked Alternaria sensitivity to both persistence and severity of asthma. In order to begin to understand genetic risk factors underlying Alternaria sensitivity and asthma, in these studies we examined T cell responses to Alternaria antigens, HLA Class II restriction and HLA-DQ protection in children with severe asthma. METHODS:Sixty children with Alternaria-sensitive moderate-severe asthma were compared to 49 children with Alternaria-sensitive mild asthma. We examined HLA-DR and HLA-DQ frequencies in Alternaria-sensitive asthmatic by HLA typing. To determine ratios of Th1/Th2 Alternaria-specific T-cells, cultures were stimulated in media alone, Alternaria alternata extract and Alt a1. Sensitivity to IL-4 stimulation was measured by up-regulation of CD23 on B cells. RESULTS:Children with Alternaria-sensitive moderate-severe asthma trended to have increased sensitivities to Cladosporium (46% versus 35%), to Aspergillus (43% versus 28%), and significantly increased sensitivities to trees (78% versus 57%) and to weeds (68% versus 48%). The IL-4RA ile75val polymorphism was significantly increased in Alternaria-sensitive moderate-severe asthmatics, 83% (0.627 allele frequency) compared to Alternaria-sensitive mild asthmatics, 57% (0.388 allele frequency). This was associated with increased sensitivity to IL-4 stimulation measured by significantly increased IL-4 stimulated CD23 expression on CD19+ and CD86+CD19+ B cells of Alternaria-sensitive moderate-severe asthmatics. IL-5 and IL-13 synthesis was significantly increased in Alternaria-sensitive moderate-severe asthmatics compared to mild asthmatics to Alternaria extract and Alt a1 stimulation. The frequency of HLA-DQB1*03 allele was significantly decreased in Alternaria-sensitive moderate-severe asthmatics compared to mild asthmatics, 39% versus 63%, with significantly decreased allele frequency, 0.220 versus 0.398. SUMMARY:In children with Alternaria-sensitive moderate severe asthma, there was an increased Th2 response to Alternaria stimulation and increased sensitivity to IL-4 stimulation. This skewing towards a Th2 response was associated with an increased frequency of the IL-4RA ile75val polymorphism. In evaluating the HLA association, there was a decreased frequency of HLA-DQB1*03 in Alternaria-sensitive moderate severe asthmatic children consistent with previous studies suggest that HLA-DQB1*03 may be protective against the development of mold-sensitive severe asthma.

Dataset Information

Association of serum TNF-?, IL-8 and free light chain with HLA-DR B alleles expression in pulmonary and extra-pulmonary sarcoidosis.

Publications

Association of serum TNF-α, IL-8 and free light chain with HLA-DR B alleles expression in pulmonary and extra-pulmonary sarcoidosis.

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