Enterocyte Autoantibodies (GECAs) and HLA: Their Relationship with HIV Infection Pathogenesis

The significance of gut epithelial cell autoantibodies (GECAs), human leukocyte antigen (HLA) alleles, and other scientifically relevant factors has been largely overlooked, despite their potential importance in the medical management of HIV-infected individuals, in understanding the pathogenesis of AIDS, and in improving epidemiological and diagnostic approaches. This review may be considered as a hypothesis-driven narrative paper mostly considering GECAs and some easily detectable genetic markers. Thus, the aim is to highlight these neglected medical and scientific issues. Addressing them may contribute to a deeper understanding of HIV pathology at both the individual and population levels. Autoantibodies against enterocytes (GECAs) are present in the majority of HIV-positive patients. These intestinal epithelial cells are crucial for nutrient absorption and because of their role as antigen-presenting cells (APCs) within the immune system. Furthermore, the number of CD4-positive lymphocytes depends largely on daily antigenic stimulation rather than on thymic function, which becomes residual or inactive after puberty. The fall of CD4+ lymphocyte counts observed in HIV-infected patients may therefore be exacerbated by enterocyte dysfunction/damage, as indicated by the presence of GECAs. These autoantibodies either cause or reflect damage to these important antigen-presenting cells, which may impair intestinal antigen presentation by their surface HLA proteins to the clonotypic T-cell receptor of lymphocytes. Additionally, the association between specific HLA alleles and a CCR5 variant affects HIV disease progression or transmission and should be considered in both adults and mother-infant pairs. In particular, HLA-B35 and HLA-B57 allelic groups have been implicated in influencing both the transmission and progression of HIV infection. Moreover, several aspects of the natural history of HIV infection remain unresolved and controversial, and these issues warrant urgent clarification. For instance, diagnostic tests are not yet standardised globally, and viral abundance in HIV-infected individuals or AIDS patients' cells may be relatively low. In summary, the neglected facets of HIV infection demand renewed investigation, particularly now that an HIV diagnosis is no longer the devastating prognosis it once was. The objective of this work is to emphasise additional factors that may influence the course of AIDS, such as enterocyte injury reflected by presence of GECAs. Ultimately, we propose that GECAs may impair enterocytes' HLA (MHC II)-mediated antigen presentation by enterocytes to CD4+ T lymphocytes (through T-cell receptors), thereby diminishing T-cell proliferation, reducing CD4+ cell numbers, and impairing immune function.