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Neuromyelitis optica (NMO) and multiple sclerosis (MS) are chronic neuro-inflammatory diseases believed to arise from complex interactions between environmental and genetic factors. Recently, single nucleotide polymorphisms (SNPs) in interleukin (IL)-2 and -7 receptor alpha genes have been identified as novel susceptibility alleles for MS in genome-wide association studies. However, similar research on NMO is limited. We aimed to investigate the association of IL2RA SNPs rs2104286 and rs12722489 and IL7RA SNP rs6897932 with Southern Han Chinese NMO and MS patients.
Frequencies of the three SNPs were examined in Southern Han Chinese mS cases (n=78), NMS cases (n=67) and controls (n=133) using sequencing-based typing.
The rs2104286G frequency in the IL2RA gene was significantly higher in NMO patients than in controls (puncorr=0.013, pcorr=0.026, OR:1.942, 95%CI:1.146-3.291).
The rs2104286 G allele in IL2RA is present at higher frequencies in NMO patients than in healthy controls within a Southern Han Chinese population.
Neuromyelitis optica (NMO) and multiple sclerosis (MS) are inflammatory demyelinating diseases of human central nervous system (CNS) with complex pathogenesis. IL-21/IL-21R regulates activation, proliferation and survival of both T cells and B cells, which are involved in the pathogenesis of NMO and MS. High levels of serum IL-21 were observed in NMO patients. However, concentration of cerebrospinal fluid (CSF) IL-21 in MS and NMO patients still remain unknown.
To detect the CSF concentration of IL-21 in NMO and MS patients and to evaluate its relationship with disease activity, particularly concerned about its impact on humoral immunity.
CSF IL-21 was detected by an enzyme-linked immunosorbent assay (ELISA) in NMO patients (n=21), MS patients (n=20) and controls (n=16).
CSF concentration of the IL-21 was noticeably elevated in NMO (p=0.012) and borderline significantly increased in MS (p=0.115). In addition, this occurrence was associated with humoral immune activity as shown by a correlation between IL-21 and complement in NMO cohort (p=0.023) and high IL-21 levels in autoantibody-positive subgroup (p=0.027).
The concentration of CSF IL-21 was noticeably elevated and might have a positive correlation with humoral immune activity in NMO.
Neuromyelitis optica (NMO) and multiple sclerosis (MS) are autoimmune diseases of the central nervous system with complex pathogeneses. NMO was once considered to be a severe variant of MS. There has been more evidence that a non-synonymous exchange (rs763361/Gly307Ser) in the gene for CD226 is linked to several autoimmune diseases including multiple sclerosis (MS). However, no studies have investigated the role of rs763361 in the pathogenesis of NMO.
The goal of our study is to evaluate the role of CD226 Gly307Ser in neuromyelitis optica (NMO) in Southern Han Chinese.
Eight-nine NMO patients, 93 relapsing-remitting multiple sclerosis (RRMS) patients, and 122 controls (CTLs) were enrolled. The rs763361 alleles of the subjects were determined by sequencing-based typing.
The results strongly support that the TT genotypes are associated with NMO but are not significantly correlated with susceptibility for MS.
CD226 Gly307Ser may correlate with risk of NMO in Southern Han Chinese.
To compare the clinical features of our sero-negative and sero-positive neuromyelitis optica (NMO) patients.
Thirty-nine patients with NMO were recruited and analyzed retrospectively. Serum aquaporin 4 (AQP4) antibody status was determined by a cell-based assay. For the sero-negative patients, cerebrospinal fluid (CSF) and serum samples were re-tested using the cell-based assay and an indirect immunofluorescence assay.
By the cell-based assay, 30 patients (76.92%, 30/39), were positive for AQP4 antibodies in serum and 37 patients (94.9%, 37/39), had a CSF-positive antibody status. Seven NMO patients (17.9%, 7/39) were sero-negative by the cell-based assay but demonstrated positive CSF results. By indirect immunofluorescence, the remaining two patients, who had no AQP4 antibodies in serum or CSF by the cell-based assay, were positive for IgG antibodies in serum, which selectively targeted the central nervous system microvessels, pia, subpia, Virchow-Robin space, kidney, and stomach. There were no significant differences between the sero-positive and sero-negative NMO groups among their demographic and clinical data.
Repeating the test using a different assay or CSF is helpful to clarify whether sero-negative NMO patients do in fact carry AQP4 antibodies.
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