Clinical and genetic markers associated with tuberculosis, HIV-1 infection, and TB/HIV-immune reconstitution inflammatory syndrome outcomes

Nathalia Beatriz Ramos de Sá (1) , Marcelo Ribeiro-Alves (1) , Tatiana Pereira da Silva (1) , José Henrique Pilotto (1, 2) , Valeria Cavalcanti Rolla (1) , Carmem Giacoia-Gripp (1) , Daniel Scott-Algara (3) , Mariza Gonçalves Morgado (1) , Sylvia Lopes Maia Teixeira (1)

1 FIOCRUZ - Fundação Oswaldo Cruz / Oswaldo Cruz Foundation
2 HGNI - Hospital Geral de Nova Iguaçu
3 Biologie Cellulaire des Lymphocytes - Lymphocyte Cell Biology

Background: Tuberculosis (TB) and AIDS are the leading causes of infectious disease death worldwide. In some TB-HIV co-infected individuals treated for both diseases simultaneously, a pathological inflammatory reaction termed immune reconstitution inflammatory syndrome (IRIS) may occur. The risk factors for IRIS are not fully defined. We investigated the association of HLA-B, HLA-C, and KIR genotypes with TB, HIV-1 infection, and IRIS onset. Methods: Patients were divided into four groups: Group 1- TB+/HIV+ (n = 88; 11 of them with IRIS), Group 2- HIV+ (n = 24), Group 3- TB+ (n = 24) and Group 4- healthy volunteers (n = 26). Patients were followed up at INI/FIOCRUZ and HGNI (Rio de Janeiro/Brazil) from 2006 to 2016. The HLA-B and HLA-C loci were typed using SBT, NGS, and KIR genes by PCR-SSP. Unconditional logistic regression models were performed for Protection/risk estimation. Results: Among the individuals with TB as the outcome, KIR2DS2 was associated with increased risk for TB onset (aOR = 2.39, P = 0.04), whereas HLA-B*08 and female gender were associated with protection against TB onset (aOR = 0.23, P = 0.03, and aOR = 0.33, P = 0.01, respectively). Not carrying KIR2DL3 (aOR = 0.18, P = 0.03) and carrying HLA-C*07 (aOR = 0.32, P = 0.04) were associated with protection against TB onset among HIV-infected patients. An increased risk for IRIS onset was associated with having a CD8 count ≤500 cells/mm3 (aOR = 18.23, P = 0.016); carrying the KIR2DS2 gene (aOR = 27.22, P = 0.032), the HLA-B*41 allele (aOR = 68.84, P = 0.033), the KIR2DS1 + HLA-C2 pair (aOR = 28.58, P = 0.024); and not carrying the KIR2DL3 + HLA-C1/C2 pair (aOR = 43.04, P = 0.034), and the KIR2DL1 + HLA-C1/C2 pair (aOR = 43.04, P = 0.034), CONCLUSIONS: These results suggest the participation of these genes in the immunopathogenic mechanisms related to the conditions studied. This is the first study demonstrating an association of HLA-B*41, KIR2DS2, and KIR + HLA-C pairs with IRIS onset among TB-HIV co-infected individuals.

Mots clés: HLA-C genes; Immune Reconstitution Inflammatory Syndrome; KIR genes; Tuberculosis; HIV-1; HLA-B genes

Domaines: Sciences du Vivant [q-bio]; Immunologie; Immunité innée

Nathalia Beatriz Ramos de Sá, Marcelo Ribeiro-Alves, Tatiana Pereira da Silva, José Henrique Pilotto, Valeria Cavalcanti Rolla, et al.. Clinical and genetic markers associated with tuberculosis, HIV-1 infection, and TB/HIV-immune reconstitution inflammatory syndrome outcomes. BMC Infectious Diseases, 2020, 20 (1), pp.59. ⟨10.1186/s12879-020-4786-5⟩. ⟨pasteur-02573664⟩