Low expression Macrophage Migration Inhibitory Factor (MIF) alleles and tuberculosis in HIV infected South Africans

Duncan Reid; Sheela Shenoi; Ravesh Singh; Max Wang; Vinod Patel; Rituparna Das; Keshni Hiramen; Yunus Moosa; Francois Eksteen; Anthony P Moll; Thumbi Ndung'u; Victoria Kasprowicz; Lin Leng; Gerald H Friedland; Richard Bucala

doi:10.1016/j.cytox.2019.100004

Low expression Macrophage Migration Inhibitory Factor (MIF) alleles and tuberculosis in HIV infected South Africans

Cytokine X. 2019 Feb 16;1(1):100004. doi: 10.1016/j.cytox.2019.100004. eCollection 2019 Mar.

Authors

Duncan Reid¹, Sheela Shenoi¹, Ravesh Singh^{2

3}, Max Wang⁴, Vinod Patel⁵, Rituparna Das⁶, Keshni Hiramen², Yunus Moosa⁷, Francois Eksteen⁸, Anthony P Moll⁸, Thumbi Ndung'u^{2

3}, Victoria Kasprowicz^{2

3}, Lin Leng¹, Gerald H Friedland^{1

4}, Richard Bucala^{1

4}

Affiliations

¹ Department of Internal Medicine, Yale School of Medicine, New Haven, CT, United States.
² HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
³ African Health Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
⁴ Yale School of Public Health, New Haven, CT, United States.
⁵ Department of Neurology, Nelson R. Mandela School of Medicine University of KwaZulu-Natal, Durban, South Africa.
⁶ Department of Internal Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, United States.
⁷ Department of Infectious Diseases, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
⁸ Church of Scotland Hospital, Tugela Ferry, KwaZulu-Natal, South Africa.

Abstract

Host immunity is crucial for controlling M. tuberculosis infection. Functional polymorphisms in the cytokine macrophage migration inhibitory factor (MIF) show global population stratification, with the highest prevalence of low expression MIF alleles found in sub-Saharan Africans, which is a population with the greatest confluence of both TB and HIV infection and disease. We investigated the association between MIF alleles and tuberculosis (TB) and HIV in South Africa. We acquired clinical information and determined the frequency of two MIF promoter variants: a functional -794 CATT_5-8 microsatellite and an associated -173 G/C SNP in two HIV-positive cohorts of patients with active laboratory-confirmed TB and in controls without active TB who were all HIV positive. We found a greater frequency of low expression MIF promoter variants (-794 CATT_5,6) among TB disease cases compared to controls (OR = 2.03, p = 0.023), supporting a contribution of genetic low MIF expression to the high prevalence of TB in South Africa. Among those with HIV, circulating MIF levels also were associated with lower CD4 cell counts irrespective of TB status (p = 0.016), suggesting an influence of HIV immunosuppression on MIF expression.

Keywords: Immune response; MIF; MIF, macrophage migration inhibitory factor gene; MIF, macrophage migration inhibitory factor protein; Macrophage; SNP, single nucleotide polymorphism; Tuberculosis.

Abstract

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