Comparison of antibody responses against Mycobacterium tuberculosis antigen Rv0679c in tuberculosis patients from the endemic and non-endemic regions of the Beijing genotype: a case control study

Abstract

BackgroundStrains of the Beijing genotype of Mycobacterium tuberculosis (MTB) are reportedly associated with the virulence of tuberculosis (TB) infection, unfavorable outcomes of anti-TB treatment, and the global TB pandemic. Rv0679c, a hypothetical membrane protein related to host cell invasion, has a Beijing genotype-specific mutation at residue 142 (Asn142Lys). Antigenicity differences between Rv0679c-Asn142 (N-type) and Rv0679c-Lys142 (K-type) have been previously observed in mice antigen-antibody responses. However, the immune response to Rv0679c in humans remains unknown. Therefore, we aimed to investigate the anti-Rv0679c immune response in TB patients from the endemic and non-endemic regions of the Beijing MTB genotype.MethodsWe analyzed the Rv0679c-specific antibody responses in 84 subjects from the endemic region of the Beijing genotype MTB in China, including 45 pulmonary TB patients (C-PTB) and 39 healthy controls (C-HC), and 81 subjects from the Philippines (the endemic region of the non-Beijing genotype), including 51 pulmonary TB patients (P-PTB) and 30 healthy controls (P-HC). Anti-tuberculous-glycolipid (TBGL) antigen was used as the control antibody.ResultsTBGL IgG titers were higher in both C-PTB and P-PTB than those in their corresponding HC (C-PTB median 4.2, P-PTB median 11.2; C-PTB vs. P-PTB, p > 0.05), suggesting immune response comparability in PTB from two different countries. C-PTB showed a higher response compared to C-HC for anti-K-type IgG (53.3%) than anti-N-type IgG (6.67%); this response was not observed in P-PTB (both N-type and K-type 9.80%).ConclusionDimorphic antigen Rv0679c was found to be associated with distinct immune response patterns, indicating the role of Beijing/non-Beijing genotype of MTB in stimulating specific responses in TB patients from the endemic region of Beijing MTB. Meanwhile, reactions to Rv0679c in patients and HC from non-endemic regions of the Beijing MTB may be caused by the response to the common epitope of Rv0679c N/K-type.

Expression of IL32 and IL33 Genes in Tuberculosis Patients

“…Mean ±Std anti TB IgG antibodies was (1.42±0.59) in comparison to controls (0.11±0.21), with highly significant differences. Zhao, et al, (2017) proved the increase in IgG titer with the chronic period in cases of TB disease in the sera of infected patients and that there is a response to antibodies compared to healthy people who are considered as controls [12]. The Mean±Std of IL-33 was (20.38±6.53) in comparison to the control group (2.28±2.48) with a highly significant difference.…”

Site-directed mutagenesis of Mycobacterium tuberculosis and functional validation to investigate potential bedaquiline resistance-causing mutations

“…The Rv0678 Thr33Ala mutant strains acquired four mutations, of which one (c.426C>G; p.Asn142Lys) was located in the Rv0679c gene which encodes an uncharacterized threonine-rich protein with an unknown function and has also not been described in relation to BDQ resistance. According to literature, this mutation has been observed in clinical isolates of the Beijing genotype and appears to influence the immune response 51 , 52 . Given that this mutation has been classified as a lineage marker, it is unlikely to affect the BDQ phenotype 53 .…”