Further we detected elevated T cell responses against antigens P0 180-199 and MBP 82-100 in CIDP patients which have not described before. We confirmed or previous findings that changes of the T memory compartment is a common finding especially in untreated patients [8, 17], which is in contrast to Sanvito and colleagues who showed no differences in T cell subpopulation [23]. cell responses against the peripheral myelin antigens of PMP-22, P2, P0 and MBP peptides compared to typical CIDP. Searching for novel auto-antigens, we found that T cell responses against P0 180-199 as well as MBP 82-100 were significantly elevated in atypical CIDP patients vs. HC. Conclusions Our results indicate differences in underlying T cell responses between atypical and typical CIDP characterized by a higher peripheral myelin antigen-specific T cell responses as well as a specific altered CD4+ memory compartment in atypical CIDP. Larger multi-center studies study are warranted in order to characterize T cell auto-reactivity in atypical CIDP subgroups in order to establish immunological markers as a diagnostic tool. Keywords: Chronic inflammatory demyelinating polyneuropathy, T memory subsets, MBP protein, P0 protein, Atypical, Typical Background Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common autoimmune peripheral neuropathy but remains a rare disease with a prevalence of 0.8-8.9 Topiroxostat (FYX 051) cases per 100.000 [1, 2]. The disorder causes severe disability in more than 50% of the patients in a chronic-progressive course [1]. Diagnosis can be difficult given the heterogeneity of CIDP phenotypes. About 50% of the patients suffer from so-called atypical variants including (DADS) in 25-35% of the cases, (MADSAM) in 15% and rare variants such as pure sensory CIDP (10-13%), pure motor CIDP (<10%) and focal CIDP (2%) [3]. These CIDP subtypes are likely to differ with respect to underlying pathomechanisms and may necessitate different treatment approaches. Despite recent progress, the underlying immunopathogenetic mechanisms remain poorly understood [4]. Both humoral as well as cellular immune responses are likely to play a role in the induction of autoimmune neuroinflammation, which leads to demyelination and axonal degeneration [4C7]. Peripheral myelin antigens are promising auto-antigens in CIDP pathogenesis. Recently, we demonstrated higher frequencies of auto-reactive IFN- responses directed against the peripheral myelin antigens PMP-22 and P2 in treatment na?ve patients who responded subsequently Topiroxostat (FYX 051) well to intravenous immunoglobulin (IVIG) treatment. Clinical improvement under IVIG-treatment correlated with the reduction of antigen-specific responses against PMP-22 and P2 [8]. Experimental studies in the EAN model of Guillain-Barr-Syndrom (GBS) support a pathogenic role of another compact myelin P0. Immunization with P0 180-199 is capable to induce EAN in wildtype-, IFN- and TNF- mice [9C11]. However, an evaluation in CIDP patients remains to be done. Myelin basic protein (MBP) is a major constituent of the myelin sheath in the central and peripheral nervous system [12]. Whereas it has been established as an immunodominant auto-antigen for demyelination in the immunopathogenesis of Multiple Sclerosis (MS) its auto-reactive potential in CIDP remains elusive [13]. T cells can be differentiated into CD45RA+ CCR7+ na?ve, CD45RA- CCR7- effector memory (TEM), CD45RA- CCR7+ central memory (TCM) and CD45RA+ CCR7-terminally differentiated effector memory (TEMRA) T cells [14]. Especially CD4+ T cells play a major role in CIDP immunopathogenesis [15C17]. In blood and CSF of CIDP patients, significantly elevated frequencies of CD4+ TEM and CD4+ TCM were demonstrated, whereas long-term treated CIDP patients showed significantly reduced CD4+ memory subsets in contrast to untreated CIDP patients [17C19]. Here, we hypothesize that autoreactive myelin-specific T cell responses as well as T cell memory subsets differ between Topiroxostat (FYX 051) atypical and typical manifestations of CIDP. Methods Patients We evaluated 26 CIDP patients using clinical and immunological (enzyme-linked Topiroxostat (FYX 051) immunospot assay ELISPOT, fluorescence-activated cell sorting FACS) examinations in comparison to 28 healthy, age-matched controls. CIDP patients who met the diagnostic criteria of European Federation of Neurological Sciences (EFNS) 2010 were divided into typical vs. atypical according to EFNS 2010 [20]. Therapy response was defined as an improvement of 2 in Medical Research Council (MRC) sum score in 2 different muscle groups, an improvement of 1 1 Goat polyclonal to IgG (H+L)(PE) in Inflammatory Neuropathy Cause and Treatment (INCAT) score.