IL-2 and Mycobacterial Lipoarabinomannan as Targets of Immune Responses in Multiple Sclerosis Patients

Abstract

Interleukin 2 (IL-2) is considered a key player in exacerbating multiple sclerosis (MS). Therapies targeting its receptor have been developed; however, a resolution of the disease and side effects are still an issue of concern. The involvement of other factors, such as Mycobacterium avium subspecies paratuberculosis (MAP) and envelope protein derived from human endogenous retrovirus type W (HERV-Wenv), in MS pathogenesis has been recently suggested. Here, we investigated the levels of antibodies (Abs) directed against IL-2 and HERV-Wenv in 108 MS patients, 34 patients affected by neuromyelitis optica spectrum disorder (NMOSD), and 137 healthy controls (HCs). Our results show increased levels of Abs specific to IL-2 and HERV-Wenv-su antigens in MS vs. HCs (p < 0.0001 for IL-2, p = 0.0004 for HERV-Wenv) and significantly decreased levels in NMOSD vs. MS. The assessment of different 12-month-long therapies on Abs against IL-2, HERV-Wenv, and MAP lipoarabinomannan (LAM) demonstrated the strongest effect on anti-LAM Abs (p = 0.018), a slight reduction of anti-IL-2 Abs, and small variations for anti-HERV-Wenv Abs. These results highlight the conclusion that the impact of therapy is more correlated with selected epitopes than with the therapeutic agent. Screening for anti-IL-2 and anti-HERV-Wenv Abs has a potential as additional future practice to distinguish between symptomatically similar MS and NMOSD.

Presence of Infection by Mycobacterium avium subsp. paratuberculosis in the Blood of Patients with Crohn’s Disease and Control Subjects Shown by Multiple Laboratory Culture and Antibody Methods

“…Mycobacterium avium subspecies paratuberculosis (MAP) is accepted as the cause of Johne’s Disease (JD) [ 1 ], a chronic diarrheal wasting disease of cattle and a wasting disease in sheep and goats [ 2 ] and has long been suspected to be involved in the etiology of Crohn’s Disease (CD), an inflammatory bowel disease (IBD) of humans [ 3 ]. MAP and/or CD are also associated with many other autoimmune diseases including multiple sclerosis (MS) [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ], type I diabetes mellitus (T1DM) [ 14 , 15 , 16 , 17 , 18 , 19 ], rheumatoid arthritis [ 20 , 21 , 22 ], Sjogren’s syndrome [ 23 ], asymmetric lateral sclerosis [ 24 ], celiac disease [ 25 ], depression [ 26 ], thyroiditis [ 27 ], and the neurodegenerative diseases including Alzheimer’s disease [ 28 ] and Parkinson’s disease [ 29 ]. A diarrheal/wasting illness associated with infection with MAP has also been reported in non-human primates [ 30 ].…”

Presence Of Infection By Mycobacterium Avium Subsp. Paratuberculosis In The Blood Of Patients With Crohn’s Disease And Control Subjects Shown By Multiple Laboratory Culture And Antibody Methods

“…Mycobacterium avium subspecies paratuberculosis (MAP) is accepted as the cause of Johne's Disease (JD) [1], a chronic diarrheal wasting disease of cattle and a wasting disease in sheep and goats [2] and has long been suspected to be involved in the etiology of Crohn's Disease (CD), an inflammatory bowel disease (IBD) of humans [3]. MAP and/or CD are also associated with many other autoimmune diseases including multiple sclerosis [4][5][6][7][8][9][10][11][12][13], type I diabetes mellitus [14][15][16][17][18][19], rheumatoid arthritis [20][21][22], Sjogren's syndrome [23], asymmetric lateral sclerosis [24], systemic sclerosis, celiac disease [25], depression [26], thyroiditis [27], and the neurodegenerative diseases including Alzheimer's disease [28] and Parkinson's disease [29]. A diarrheal/wasting illness associated with infection with MAP has also been reported in non-human primates [30].…”

A Comparative and Comprehensive Review of Antibody Applications in the Treatment of Lung Disease

“…Pérol L, et al have already shown the existence of anti-I autoantibodies in non-obese diabetic mice and Type 1 Diabetes patients, and the IL-2 m serve as an autoimmune target for patients with Type 1 Diabetes [97]. This is not o because IL-2 serves a role in autoimmune disease [98,99], but also due to its regulat role for Anti-inflammatory T regulatory cells (Treg) regulation, since IL-2 can control immune response by maintaining Treg cell function and promoting immune response stimulating classic T cells [100]. Importantly, the correlation between low survival a Treg infiltration in the tumor microenvironment has been well established.…”