It is long-established that pathogenesis of many autoimmune diseases is mainly promoted by inadequate immune responses to bacterial agents, among them Mycobacterium tuberculosis. Tuberculosis is a multifaceted process having many different outcomes and complications. Autoimmunity is one of the processes characteristic of tuberculosis; the presence of autoantibodies was documented by a large amount of evidence. The role of autoantibodies in pathogenesis of tuberculosis is not quite clear and widely disputed. They are regarded as: (1) a result of imbalanced immune response being reactive in nature, (2) a critical part of TB pathogenicity, (3) a beginning of autoimmune disease, (4) a protective mechanism helping to eliminate microbes and infected cells, and (5) playing dual role, pathogenic and protective. There is no single autoimmunity-mechanism development in tuberculosis; different pathways may be suggested. It may be excessive cell death and insufficient clearance of dead cells, impaired autophagy, enhanced activation of macrophages and dendritic cells, environmental influences such as vitamin D insufficiency, and genetic polymorphism, both of Mycobacterium tuberculosis and host.
1. Introduction
Tuberculosis (TB), a dangerous chronic infectious disease caused by
Mycobacterium tuberculosis (Mtb), is still a threat to public health worldwide. A global total of around 10 million people became ill with TB in 2020 [
1]. Drug resistance of Mtb [
2], HIV infection, malnutrition, especially vitamin D deficiency, aging, autoimmune diseases, and abundant usage of immune suppressants contribute to increased incidence of TB [
3].
Epidemiological studies associate microbial infections and autoimmunity (AI), hypothesizing infections to be able to trigger autoimmune diseases (AID) [
4,
5,
6]. A number of studies have shown sera from patients with active TB to contain autoantibodies (AAB). TB has many different outcomes and complications. Autoimmunity (AI) is one of the processes characteristic of TB; at least, the presence of AABs was documented by a large amount of evidence. AABs, being typical for autoimmune disorders, are also present in different infectious diseases [
5,
6,
7,
8]. The role of AABs in the pathogenesis of TB development is widely disputed. They are considered (1) as a result of imbalanced immune response being reactive in nature [
9,
10,
11]; (2) as a critical part of TB pathogenicity, leading to cavitation and transmission [
12]; (3) as a beginning of AI disease [
12,
13]; (4) as a protective mechanism helping to dispose of microbes and infected cells [
14]; and (5) as playing a dual role, pathogenic and protective [
14]. Such diverse opinions lead to the conclusion that mechanisms involved may vary in each case. Mtb can trigger different pathways of the immune responses.
Several possible mechanisms of AI development in TB may be suggested. It may be excessive cell death and insufficient clearance of dead cells, impaired autophagy, enhanced activation of macrophages (Mphs) and dendritic cells (DCs), environmental influences such as vitamin D insufficiency, and genetic polymorphism, both of Mtb and host. Chronic presence of infection can be regarded as an endogenous adjuvant [
15]. With the existence of different pathways of immune responses, the one receiving the support from additional factors dominates. Multiple surface Mtb molecules can differently orchestrate immune responses.
2. Occurrence of AABs in Active TB Patient Sera
Early reports have established links between Mtb and AI [
7,
8,
70,
71]. A number of studies connecting TB with AI investigated the AAB characteristics of AIDs. The list of AABs includes rheumatoid factor (RF), antinuclear antibodies (ANA), anti-dsDNA AAB, anticardiolipin antibody (ACA; IgM isotype predominant), antineutrophil cytoplasmic antibodies (ANCA), and anticyclic citrullinated peptide (anti-CCP) [
8,
9,
11,
48,
50,
72,
73,
74,
75,
76,
77,
78] (
Table 1).
Table 1. The autoantibodies in tuberculosis.
AAB Type |
AAB in AIDs |
AAB in TB (References) |
rheumatoid factor (RF) |
rheumatoid arthritis, Sjögren’s syndrome |
[7,11,76] |
antinuclear antibodies (ANA) |
SLE, Sjögren’s syndrome, scleroderma, dermatomyositis |
[7,8,70,72,73] |
anti-dsDNA antibodies |
SLE |
[10,11,48,50,77] |
antineutrophilic cytoplasmatic antibodies (ANCA) |
ANCA-associated systemic vasculitis |
[11,74,75] |
anticyclic citrullinated peptide (anti-CCP) |
rheumatoid arthritis |
[76] |
anti-Scl-70, antihistone antibodies |
systemic sclerosis, SLE |
[10] |
antiphospholipid antibodies (aPL): the lupus anticoagulant (LA), anticardiolipin antibody (ACA), anti-beta 2 glycoprotein 1 (anti-ß2 GPI), anti-prothrombin |
antiphospholipid syndrome, SLE |
[21,22,24] |
anticardiolipin antibody (ACA; IgM) |
SLE, antiphospholipid syndrome |
[8,10,11,50] |
antibodies against β2 glycoprotein IgG |
antiphospholipid syndrome, SLE |
[11] |
antibodies against proteinase 3, myeloperoxidase, bactericidal/permeability-increasing protein, lactoferrin |
systemic vasculitis |
[21] |
This entry is adapted from the peer-reviewed paper 10.3390/pathophysiology29020022