HLA I and HLA II are associated with?

By SWA

 As a person with Psoriasis, Herpes, Candida, and Rheumatoid Arthritis
 

I collected a summary from several publications. 

 Psoriasis: both HLA I (Human Leukocyte Antigen class I) and HLA II (Human Leukocyte Antigen class II) are associated with psoriasis, a chronic autoimmune skin condition.

  1. HLA-Cw6 (a HLA Class I Antigen): This is the most significantly associated allele with psoriasis, especially with early-onset psoriasis. Individuals carrying HLA-Cw6 have a higher risk of developing psoriasis and it is thought to be involved in the pathogenesis of the disease.

  2. HLA Class II Antigens: While the association is stronger with HLA Class I antigens, certain HLA Class II alleles have also been implicated in psoriasis. These alleles might not be as strongly associated with the disease as HLA-Cw6, but they contribute to the genetic susceptibility and variability in the disease presentation. 

    HLA I and EBV

    HLA Class I Molecules and T Cells: HLA Class I molecules present viral antigens to CD8+ T cells. In the case of EBV, which is a herpesvirus, the infected cells present EBV antigens via HLA Class I molecules to the cytotoxic T cells. This is crucial for the immune system to recognize and eliminate EBV-infected cells.

    EBV and HLA Association: Certain HLA Class I alleles have been associated with an increased or decreased risk of diseases related to EBV, such as infectious mononucleosis or certain types of cancers (like nasopharyngeal carcinoma). This suggests that the variation in HLA Class I can influence the susceptibility and immune response to EBV.

    HLA II and Candida:

    HLA Class II Molecules and T Cells: HLA Class II molecules present antigens to CD4+ T helper cells. In the context of a Candida infection, antigens from the fungus are presented by HLA Class II molecules to T helper cells, initiating an immune response aimed at controlling and eliminating the infection.

    Candida and HLA Association: Certain HLA Class II alleles might influence the susceptibility to and severity of Candida infections. For instance, specific HLA-DR alleles have been linked to either increased susceptibility or resistance to systemic candidiasis.

     

    The observation that specific HLA alleles might predispose individuals to certain autoimmune conditions or chronic infections, such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), is supported by several research findings:

    HLA Associations in ME/CFS: A study focused on high-resolution genotyping of various HLA alleles in 426 Norwegian ME/CFS patients revealed significant associations. Two independent HLA associations were discovered, tagged by the alleles HLA-C07:04 and HLA-DQB103:03. These alleles were carried by 7.7% and 12.7% of ME/CFS patients, respectively. The proportion of individuals carrying one or both of these alleles was higher in the patient group compared to the control group. This finding points toward the involvement of the immune system in ME/CFS pathogenesis.

    1. HLA Alleles and Autoimmune Diseases: There are long-observed associations between specific HLA alleles and susceptibility to or protection from autoimmune diseases. Allele-specific antigen presentation (AP) has been widely proposed as a mechanism, but it's also noted that HLA molecules might have non-AP, disease-modulating effects. For instance, different HLA-DRB1 alleles known to associate with autoimmune disease risk or protection can differentially activate macrophage polarization, influencing immune responses​

    2. Specific HLA-DRB1 Alleles and Disease Risk: In Rheumatoid Arthritis (RA), the majority of affected individuals carry HLA-DRB1 alleles that code for a susceptibility epitope. These alleles are also associated with other conditions like type 1 diabetes, autoimmune hepatitis, and psoriatic arthritis. Conversely, HLA-DRB1 alleles that encode a protective epitope significantly reduce the risk for RA and other autoimmune conditions. This indicates a complex relationship between HLA alleles and various autoimmune diseases, suggesting that the presence of specific HLA alleles can either increase susceptibility to or offer protection from these conditions​

    3. HLA Alleles in Chronic Viral Infections: In chronic viral infections, cytotoxic CD8 T lymphocytes (CTLs) are crucial for eliminating pathogen-infected cells. However, during prolonged chronic infections, CTLs often lose effector function, leading to what is known as T cell exhaustion. The variation in HLA alleles can influence the induction of inhibitory pathways that lead to CTL exhaustion in chronic viral infections like HIV, HCV, and HBV. Understanding these mechanisms is vital for developing potential immune-based interventions for such chronic infections.
       

      Reference: 

      HLA-DRB1 allelic epitopes that associate with autoimmune disease risk or protection activate reciprocal macrophage polarization

      Association of HLA-alleles with the immune regulation of chronic viral infections

       

     

     

     



 

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