Ultraviolet radiation intensity predicts the relative distribution of dermatomyositis and anti–Mi‐2 autoantibodies in women

Abstract

Objective-Because studies suggest that ultraviolet radiation (UVR) modulates myositis phenotype and Mi-2 autoantigen expression, we conducted a retrospective investigation to determine if UVR may influence the relative prevalence of dermatomyositis and anti-Mi-2 autoantibodies in the United States.Methods-We assessed the relationship between surface UVR intensity in the state of residence at the time of onset with the relative prevalence of dermatomyositis and myositis autoantibodies in 380 myositis patients from referral centers in the U.S. Myositis autoantibodies were detected by validated immunoprecipitation assays. Surface UVR intensity was estimated from UV index data collected by the U.S. National Weather Service.Results-UVR intensity was associated with the relative proportion of patients with dermatomyositis (odds ratio [OR] 2.3, 95% confidence interval [CI] 0.9-5.8) and with the proportion of patients expressing anti-Mi-2 autoantibodies (OR 6.0, CI 1.1-34.1). Modeling of these data showed that these associations were confined to women (OR 3.8, respectively) and suggests that gender influences UVR effects on autoimmune disorders. Significant associations were not seen in men, nor were UVR levels related to the presence of anti-synthetase or anti-signal recognition particle autoantibodies.Conclusion-This first study of the distribution of myositis phenotypes and UVR exposure in the United States showed that UVR may modulate the clinical and immunologic expression of autoimmune disease in women. Further investigation of the mechanisms by which these effects are produced may give insights into pathogenesis and suggest therapeutic or preventative strategies.Current evidence suggests that autoimmune diseases result from environmental exposures in genetically susceptible individuals and ultraviolet radiation (UVR) is an environmental exposure of increasing interest (1). Beyond UVR's recognized association with skin cancer are other immunomodulatory effects possibly related to the development of immune- Furthermore, studies suggest that UVR regulates levels of the dermatomyositis-specific Mi-2 autoantigen via protein translational effects (4).The idiopathic inflammatory myopathies (IIM) are acquired systemic autoimmune conditions that share chronic muscle weakness due to chronic muscle inflammation. The two major clinical groups, dermatomyositis (DM) and polymyositis (PM), are distinguished by the presence of photosensitive pathognomonic rashes in DM (5). These two forms of IIM share some genetic risk factors but differ in others and appear to have distinct pathogeneses (5). Categorizing myositis patients by the presence or absence of myositis-specific autoantibodies (MSA) results in more homogenous groups in terms of epidemiology, clinical presentations, genetics and prognoses (5). MSA include autoantibodies directed against aminoacyl-tRNA synthetases (anti-synthetases), the signal recognition particle (anti-SRP), and autoantibodies that react with a 240 kD protein called chromodomain helicase DNA bi...

Sex differential association of dermatomyositis with Sjögren syndrome

“…The differential association of Sjögren syndrome between male and female patients with dermatomyositis may be explained by the different pathogenesis of dermatomyositis in the different sexes. Past studies of dermatomyositis showed sex differences in risk factors 22 and autoantibody profiles. 24 Furthermore, genetic studies of pediatric dermatomyositis showed sexual dimorphism in the gene-gene interaction.…”

“…20,21 It is important to gain a more accurate understanding of this increased risk of Sjögren syndrome in dermatomyositis. Although research into dermatomyositis showed sex differences in risk factors, 22 cytokine expression, 23 autoantibodies profile 24 and certain dermatomyositis-related outcomes, 2 it is unknown whether the association with Sjögren syndrome differs among men and women with dermatomyositis.…”

Special papers Diagnostic and therapeutic advances in dermatomyositis

“…Pacjenci z tym rodzajem przeciwciał mają typowe dla DM zmiany skórne, takie jak objaw i/lub grudki Gottrona, rumień heliotropowy, rumień i rozrost obrąbka naskórkowe-go paznokcia, zmiany rumieniowe dotyczące podstawy karku, dekoltu, górnej części pleców i ramion (rumień w kształcie litery V i objaw szala). Występo-wanie przeciwciał anty-Mi-2 wiąże się ze szczególnie nasiloną fotowrażliwością, a u kobiet ich miano dodatnio koreluje z pochłoniętą dawką promieniowania ultrafioletowego [1,20]. Pacjenci, u których stwierdza się przeciwciała anty-Mi-2, mają mniej nasilone objawy mięśniowe, znacznie rzadziej zajęcie płuc oraz zapalenie stawów i zazwyczaj dobrze odpowiadają na leczenie glikokortykosteroidami (GKS).…”

Non-Bone Effects of Vitamin D in Children, Adolescents, and Young Adults

“…There are number of conflicting hypotheses which indicate that differences in the amount of adipose tissue in males and females and in their skins may lead to the variation in vitamin D synthesis. Number of studies has demonstrated decreased bioavailability of fat soluble vitamin D3 from cutaneous and dietary sources because of its deposition in body fat [24][25][26][27]. This may point toward decreased vitamin D levels in women because of their excessive adiposity as compared to men.…”

“…Individuals who have the GSTM1 null genotype and are missing the enzyme may, therefore, be at an increased risk of DNA damage and can induce the onset of lupus [122]. Work done by Love et al to study the distribution of myositis phenotypes and ultraviolet radiation exposure in the United States showed that ultraviolet radiation may modulate the clinical and immunological expression of autoimmune disease in women [123]. The above evidence points toward the stimulation and exacerbation of autoimmune process in specific disease, whereas, on the other hand, ultraviolet radiations can also prevent or reduce the symptoms of other autoimmune diseases by vitamin D formation in skin as elaborated in various parts of this chapter.…”