Geographical Latitude Remains as an Important Factor for the Prevalence of Some Myositis Autoantibodies: A Systematic Review

Abstract

The idiopathic inflammatory myopathies (IIM) are characterized by muscular weakness, cutaneous manifestations, muscle damage revealed by increase of muscular enzymes, muscle biopsy, electromyography and changes on magnetic resonance imaging. However, the hallmark of these IIM, is the development of myositis specific antibodies (MSA) or myositis associated antibodies (MAA). The theories about their presence in the serum of IIM is not known. Some studies have suggested that some of these MSA, such as anti-Mi-2 increases according to the intensity of UV radiation. There is scarce information about the environmental factors that might contribute in order to be considered as triggering factors as UV radiation might be. In this review, we analyzed the reported prevalence of MSAs and MAAs regarding to their geographical location and the possible relation with UV radiation. We collected the prevalence data of fifteen MSA and thirteen MAA from 22 countries around the world and we were able to observe a difference in prevalence between countries and continents. We found differences in anti-PL7, anti-Ro52, anti-La and anti-Ku prevalence according to UV radiation level. Otherwise, we observed that anti-Mi-2 prevalence increases near to the Equator meanwhile anti-MJ/NXP2 and anti-ARS prevalence had an opposite behavior increasing their prevalence in the geographical locations farther to the Equator. Our results highlighted the importance to include the UV radiation and other environmental factors in IIM studies, in order to clarify its association with MSA and MAA prevalence as well as its possible role in the immunopathogenesis of these diseases.

Keywords: UV radiation; autoantibodies; idiopathic inflammatory myopathies (IIM); latitude; prevalence.

Figure 1

Subgroups of IIM according to autoantibody phenotype. Not all autoantibodies are exclusive for the myopathy subgroup, as is the case of anti-Signal Recognition Particle (SRP) that might be found in polymyositis (PM) and immune-mediated necrotizing myopathy (IMNM). Notwithstanding, anti-hydroxymethylglutaryl coenzyme A reductase (HMGCR) is classically observed in IMNM. The anti-aminoacyl tRNA synthetase (ARS) autoantibodies are related to anti-synthetase syndrome (ASSD). Inclusion body myositis (IBM) is associated but not exclusive for anti-cytosolic 5’nucleotidase 1A (cN1A). Dermatomyositis (DM) is associated to cancer development in positive patients for anti-Transcription Intermediary Factor 1γ/α (TIF1γ/α). Anti-Mi-2, Nuclear Matrix Protein 2 (NXP2) and anti-Small ubiquitin-like modifier Activating Enzyme (SAE) are also related to DM. The presence of anti-Melanoma Differentiation-Associate Gene 5 (MDA5) is associated with rapidly progressive interstitial lung disease (RPILD) in amyopathic dermatomyositis (ADM).

Figure 2

PubMed and MeSH database PRISMA flow diagram. Three key aspects were considered in our database search: myositis (myositis, polymyositis, inclusion body myositis or dermatomyositis), geographical location (epidemiology or geographic location) and antibodies (antibodies or anti-Mi-2). However, the only screened records were those papers related to the three important aspects in our search (n = 242). Finally, 150 of them were excluded and 92 were considered and reviewed in this study.

Figure 3

Correlation of anti-Mi-2 prevalence in all IIM subgroups with (A) latitude; (B) mean annual UV radiation; (C) median annual UV radiation; (D) minimum annual UV radiation, and; (E) maximum annual UV radiation.

Figure 4

Anti-Mi-2 global prevalence in all IIM subgroups. We classified all our data per countries and according to geographic locations to obtain anti-Mi-2 prevalence. The map shows that the anti-Mi-2 prevalence increases in the geographic zone closer to the Equator and decreases in the locations farther to the Equator; likewise, UV radiation increases according to Equator proximity and it is different between geographic locations (P < 0.001). ^#UV annual average radiation, we only considered the colored countries in the map. ^$Non-parametric test, asymptotic significance. * (9). ** (6). NR: No Reported prevalence of anti-Mi-2 in these countries. Map image was made at: (https://mapchart.net/world.html).

Figure 5

Differences of autoantibodies prevalence between geographical locations. (A) Anti-Mi-2 showed an increase in the geographical region closer to the Equator and a decrease in those farther to the Equator; (B) anti-MJ/NXP2 and (C) anti-ARS prevalence had an opposite behavior increasing in the geographical locations farther to the Equator.

Figure 6

Correlation of geographical latitude and mean UV radiation with (A) anti-Ro52; (B) anti-PL12 and; (C) anti-PMScl-75 in all IIM subgroups.