As EBV infects naive B cells in mucosal surfaces exposed to fungi, forbidden memory B cells targeting fungal epitopes could be produced (55)

As EBV infects naive B cells in mucosal surfaces exposed to fungi, forbidden memory B cells targeting fungal epitopes could be produced (55). with a fungal etiology. Future microbiome and serological studies should consider fungi as a possible risk factor for MS, and future clinical studies should consider the effect of fungicides other than DMF on MS symptoms. in the gut is associated with psoriasis (14, 15) and Crohns disease (16, 17). Antibodies against fungi are a risk factor of psoriasis (18, 19), and fungicides improve symptoms (20). Antibodies against fungal mannoproteins are a risk factor of ankylosing spondylitis (21), systemic lupus erythematosus (22, 23), sarcoidosis (24), and Crohns disease (25). Few groups have considered a role for fungi in MS. In 1981, Truss reported the resolution of symptoms in five MS cases following antifungal therapy (26). In 2008, Ramos and colleagues reported finding serum antibodies against in seven out of eight MS patients, while finding none in 10 healthy controls (27). In 2010 2010, this association was replicated in a larger case-control study (28), and again in 2013 in a small case-control study that linked anti-antibodies in the cerebrospinal fluid (CSF) to MS (29). In this review, we analyze the evidence linking MS to a possible fungal etiology. Genetic Susceptibility The HLA-DRB1*15 allele group is the strongest genetic risk factor of MS (7). Of the three common HLA-DRB1*15 alleles, HLA-DRB1*1501 and HLA-DRB1*1503 are associated with MS, while HLA-DRB1*1502 is not (7). These three alleles are very similar: as compared to HLA-DRB1*1501, HLA-DRB1*1502 Isoliensinine substitutes valine for Isoliensinine glycine at position 86, and HLA-DRB1*1503 substitutes tyrosine for histidine at position 30 (7). HLA-DRB1*1501 and HLA-DRB1*1503 are two of many alleles forming half of the HLA-DR protein complex, which holds peptides collected by antigen-presenting cells (monocytes, macrophages, dendritic cells, and B cells) for presentation to CD4+ T cells. They thus play a key role in determining which antigens induce a T cell mediated immune response, as well as which antigens warrant naive B cell maturation into memory B cells. The HLA-DRB1*15 allele group is an important risk factor in many other inflammatory conditions, some of which are suspected of having a fungal etiology (Table ?(Table1).1). Allergic bronchopulmonary aspergillosis (ABPA) is caused by an abnormal immune response against usually benign fungi which are often present in the airways (30). The HLA-DRB1*15 alleles associated with ABPA match those associated with MS: HLA-DRB1*1501 and HLA-DRB1*1503, but not HLA-DRB1*1502 (30, 31). Pulmonary sarcoidosis is suspected of being caused by an immune response to fungal antigens in the airways (32). Granulomatous prostatitis can be caused by fungal infections, though most cases are idiopathic (33); the recent discovery of a fungicidal protein in the prostate (34) suggests a fastidious fungal infection is present in this site (35, 36). Uveitis Isoliensinine can be caused by different infectious agents, but in most cases none can be found (37). Uveitis EBI1 is associated with various idiopathic inflammatory diseases including ankylosing spondylitis, Beh?ets disease, sarcoidosis, and Crohns disease (37); it is also associated with MS, and often coincides with MS onset (38). Several studies have linked idiopathic uveitis with fungal infections (Table ?(Table11). Table 1 Inflammatory conditions associated with HLA-DRB1*15. (39)Caused by abnormal immune response against antigens (44). Mannan causes uveitis in animal model (45). Associated with chronic prostate inflammation (46, 47)(27C29)Dimethyl fumarate is effective (48), and has antifungal properties (49)species are associated with MS (27C29). With the.