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 atypical and typical manifestations of CIDP. Methods Patients We evaluated 26 CIDP patients using clinical and immunological (enzyme-linked immunospot assay ELISPOT, fluorescence-activated cell sorting FACS) examinations in comparison to 28 healthy, age-matched controls. memory T cells (TCM) as well as a tendency of higher T cell responses against the peripheral myelin antigens of PMP-22, P2, P0 and MBP peptides compared to typical CIDP. LY 344864 racemate 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 LY 344864 racemate 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. (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%) . 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 . 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 well to intravenous immunoglobulin (IVIG) treatment. Clinical improvement under IVIG-treatment correlated with the reduction of antigen-specific responses against PMP-22 and P2 . 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 . 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 . 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 . 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 LY 344864 racemate CIDP patients [17C19]. Here, we hypothesize that autoreactive myelin-specific T cell responses as well as T cell memory subsets differ between atypical and typical manifestations of CIDP. Methods Patients We evaluated 26 CIDP patients using clinical and immunological (enzyme-linked 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 . 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 in Inflammatory Neuropathy Cause and Treatment (INCAT) score (excluding changes LY 344864 racemate in arm function from 0 to 1 1) or alternatively an improvement of 50% of the walking distance as described previously . Patients and controls were recruited in the outpatient clinic of the Department of Neurology, Charit University Medicine Berlin. Peripheral myelin antigens ELISPOT assay was performed using peptides of seven peripheral myelin antigens and CEF as positive control for T cell responses (Table ?(Table1).1). CEF H4 is a peptide pool containing 23 MCH class 1 restricted viral antigens . Peripheral myelin antigens were provided by Dr. R. Volkmer, Institute of Medical Immunology, Charit University Medicine Berlin. CEF was provided by JPT Peptide Technologies GmbH, Berlin. Table 1 ELISPOT-antigens thead th rowspan=”1″ colspan=”1″ antigen /th th rowspan=”1″ colspan=”1″ Sequence /th /thead PMP-22 32C51NGHATDLWQNCSTSSSGNVHPMP-22 51C64HHCFSSSPNEWLQSPMP-22120C133RHPEWHLNSDYSYGP2 14C25ENFDDYMKALGVP2 61C70EISFKLGQEFP0 180-199ASKRGRQTPVLYAMLDHSRSMBP 82-100DENPVVHFFKNIVTPRTPPCEFpeptide pool Open in a separate window Cryopreservation of Peripheral Blood Monocytes (PBMC) To evaluate T cell responses efficiently we preserved PBMC in liquid nitrogen over a maximum of 6?months. Blood was LY 344864 racemate sampled in CPT tubes for ELISPOT and in EDTA tubes.