Zonal Tuberculosis and Chest Disease Center, Thailand
Received Date: February 05, 2014; Accepted Date: February 07, 2014; Published Date: February 08, 2014
Citation: Cheepsattayakorn A (2014) Severe Acute Respiratory Syndrome in Association with Human Leukocyte Antigen and Clinical Implications. Poult Fish Wildl Sci 2:e106. doi: 10.4172/2375-446X.1000e106
Copyright: © 2014 Cheepsattayakorn A. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Human leukocyte antigen (HLA) is the most polymorphic genetic system in humans, with numerous alleles, and subsequently, various possible combinations . These genes, the products of histocompatibility complex (MHC)  are located in the short arm of chromosome 6 at band p 21.3  and are divided into three classes, I, II and III . HLA class I is responsible for coding the molecules HLA-A, -B and -C, present in almost all somatic cells with killing of viral infected targets by class I antigens restrict cytotoxic T-cell (CD8+) function  while HLA class II genes code the molecules HLA-DR, -DQ and -DP  by presentation of exogenous antigens to T-helper cells (CD4+) or antigen presenting cells (APC) . This polymorphism contributes to the differences in susceptibility to diseases among genetically distinct groups . The molecules coded for by the HLA system are responsible for the antigen presentation . The T lymphocytes that are linked to HLA molecules only recognize antigens by the antigen-specific cell surface receptor-antigens interaction , thus the HLA antigens  and MCH molecules  apparently participate in controlling susceptibility and resistance to various diseases. Some infectious diseases were considered as familial before the finding of the causative microorganism and early twin studies indicated that there was a substantial host genetic influence on susceptibility to diseases such as polio and tuberculosis (TB) . At present, it has been confirmed that human genetic variation demonstrates a major influence on the course of diseases caused by several infectious microorganisms .
Itoyama reported that the deletion of the 287 bp Alu repeat (D allele) in intron 16 of the angiotensin converting enzyme 2 (ACE 2) gene is associated with hypoxemia and diffuse alveolar damage in patients with severe acute respiratory syndrome (SARS)  and may protect acute lung injury and respiratory failure . Nevertheless, there may be potential confounders to a genetic association study as the following: 1) the dead patients were excluded from this study, 2) hypoxemia was defined as requiring oxygen supplementation, and 3) only 44 patients were studied . Some HLA subtypes, particularly HLA-B*0703 and HLA-DRB1*0301 alleles have been demonstrated to be more prevalent in patients with SARS  and those with poorer outcomes . On the other hand, the polymorphism in ACE II gene, coding for a functional receptor of the SARS-coronavirus, was not associated with the susceptibility or outcome of SARS . A previous study revealed that CXCL10(-938AA) gene is always protective from SARS infection whenever it appears only jointly with either Fg12(+158T/*) or HO-1 (-497A/*), whereas Fg12(+158T/*) is associated with higher SARSinfection susceptibility unless combined with CXCL10/IP-10(-938AA) which is associated with lower susceptibility . Chan concluded that the ACE I/D polymorphism was not directly associated with increasing susceptibility to SARS-coronavirus infection and was not associated with poor outcome after SARS-coronavirus infection . A recent study in Taiwan demonstrated that HLA-Cw*1502 , -DR*0301 , and -A*2402  alleles conferred resistance against SARS infection. CD209L homozygote individuals  and low-mannosebinding- lectin-producing genotypes  have been demonstrated to have a significantly lower risk and increased risk of SARS infection, respectively. A previous study among Vietnamese population with SARS revealed that polymorphisms of two interferon-inducible genes, 2′,5′-oligoadenylate synthetase 1 (OAS-1 (G-allele in exon 3 and the one in exon 6)) and myxovirus resistance-A (MxA) were associated with SARS infection . The single nucleotide polymorphisms (SNPs) in MxA was associated with the progression of SARS . The SNPs in OAS-1 were associated with SARS-coronavirus infection or SARS development . The GG genotype and G-allele of G/TSNP at position -88 in the MxA gene promoter were demonstrated more frequent in hypoxemic group of patients with SARS than nonhypoxemic group . They may be related to the response of SARS patients to interferons (IFNs), particularly those with AA genotype of the A/G-SNP in exon 3 of OAS-1 may respond to IFN treatment more effectively than those with AG or GG genotype . If SARS re-emerges, IFN could be a promising candidate to treat patients with SARS [16-23]. These findings may contribute to the perception of IFN-induced antiviral response to SARS infection. SARS-coronavirus infection elicited both CD4+ and CD8+ T-cell responses to the M protein in recovered SARS patients that persisted for a long period of time . This may have significant implications in developing SARS vaccines . A previous study indicated that a HLA-A*0201- restricted decameric epitope P15 (S411-420, KLPDDFMGCV) derived from the S protein that was found to localized within the angiotensinconverting enzyme 2 receptor-binding region of the S1 domain could significantly enhance the expression of HLA-A*0201 molecules on the T2 cell surface . P15 then stimulated IFN-γ-producing cytotoxic-T lymphocytes (CTLs) from the peripheral blood mononuclear cells of former SARS patients and induced specific CTLs from P15-immunized HLA-A*2.1-transgenic mice in vivo . Significant P15-specific CTLs then were induced by HLA-A*2.1-trangenic mice that was immunized by a deoxyribonucleic-acid (DNA) vaccine encoding the S protein . This suggested that P15 was a naturally processed epitope . Thus, P15 could be a novel SARS-associated coronavirus-specific epitope and a potential target for evaluation of candidate SARS vaccines and characterization of virus control mechanisms .