Atypical type of familial Mediterranean fever: An underdiagnosed cause of chronic aseptic meningitis

ArticleNeurology and clinical neuroscience. 6(6): 191-193 (2018)journal articl

MEFV gene mutations in neuro-Behçet's disease and neuro-Sweet disease

ArticleAnnals of clinical and translational neurology. 6(12): 2595-2600 (2019)journal articl

Diagnostic approach for patients with unidentified fever according to the classical criteria of fever of unknown origin in the field of autoimmune disorders

ArticleImmunological medicine. 42(4): 176-184 (2019)journal articl

Long-term maintenance of the mucosal healing induced by azacitidine therapy in a patient with intestinal Behçet's-like disease accompanied with myelodysplastic syndrome involving trisomy 8

ArticleImmunological medicine. 42(3): 135-141 (2019)journal articl

Identification of Disease-Promoting HLA Class I and Protective Class II Modifiers in Japanese Patients with Familial Mediterranean Fever

Objectives: The genotype-phenotype correlation of MEFV remains unclear for the familial Mediterranean fever (FMF) patients, especially without canonical MEFV mutations in exon 10. The risk of FMF appeared to be under the influence of other factors in this case. The contribution of HLA polymorphisms to the risk of FMF was examined as strong candidates of modifier genes. Methods: Genotypes of HLA-B and -DRB1 loci were determined for 258 mutually unrelated Japanese FMF patients, who satisfied modified Tel-Hashomer criteria, and 299 healthy controls. The effects of carrier status were evaluated for the risk of FMF by odds ratio (OR). The HLA effects were also assessed for clinical forms of FMF, subsets of FMF with certain MEFV genotypes and responsiveness to colchicine treatment. Results: The carriers of B?39:01 were increased in the patients (OR = 3.25, p = 0.0012), whereas those of DRB1?15:02 were decreased (OR = 0.45, p = 0.00050), satisfying Bonferroni\u27s correction for multiple statistical tests (n = 28, p<0.00179). The protective effect of DRB1?15:02 was completely disappeared in the co-existence of B?40:01. The HLA effects were generally augmented in the patients without a canonical MEFV variant allele M694I, in accordance with the notion that the lower penetrance of the mutations is owing to the larger contribution of modifier genes in the pathogenesis, with a few exceptions. Further, 42.9% of 14 colchicine-resistant patients and 13.5% of 156 colchicine-responders possessed B?35:01 allele, giving OR of 4.82 (p = 0.0041). Conclusions: The differential effects of HLA class I and class II polymorphisms were identified for Japanese FMF even in those with high-penetrance MEFV mutations

Familial Mediterranean Fever Is Important in the Differential Diagnosis of Recurrent Aseptic Meningitis in Japan

ArticleInternal Medicine. 59(1): 125-128 (2020)journal articl

Clinical and Serial MRI Findings of a Sialidosis Type I Patient with a Novel Missense Mutation in the NEU1 Gene

The case of a Japanese sialidosis type I patient with a novel NEU1 gene mutation is described. The patient developed an unsteady gait at age 14 and was referred to our hospital at age 16. On admission, subnormal intelligence, dysarthria, myoclonus, intentional tremors, limb and gait ataxia, hyperreflexia and macular cherry-red spots were observed. An enzymological analysis revealed a primary deficiency of neuraminidase. An NEU1 gene analysis identified two heterozygous missense mutations: p.P80L and p.D135N. The p.D135N mutation is a novel mutation that is considered to be associated with the mild clinical phenotype of sialidosis. Serial brain MRI showed diffuse brain atrophy progressing rapidly over the 41-month observation period.ArticleINTERNAL MEDICINE. 52(1):119-124(2013)journal articl

The impact of normal serum complement levels on the disease classification and clinical characteristics in systemic lupus erythematosus

Abstract Background Some patients have normal levels of complement during the diagnosis of systemic lupus erythematosus (SLE), although decreased serum levels of complement are a hallmark of the active phase of the disease. This study investigated the clinical characteristics, impact on the classification of SLE, and the prognosis of patients with SLE who had normal serum complement levels at initial diagnosis (N-com). Methods We evaluated 21 patients with N-com and 96 patients with hypocomplementemia at the initial diagnosis of SLE (H-com). The classification rates among the American College of Rheumatology (ACR) 1997, Systemic Lupus International Collaborating Clinics (SLICC) 2012, European League Against Rheumatism (EULAR)/ACR 2019 criteria, and clinical and immunological involvements were compared between SLE patients with N-com and H-com. Relapse and organ damage based on the SLICC/ACR damage index were also evaluated. Results The classification rates of SLE were not significantly different in the ACR, SLICC, and EULAR/ACR criteria between the N-com and H-com groups. Patients with N-com had no significant differences in the classification rates among the three criteria, whereas patients with H-com had lower classification rates in the ACR criteria than in the SLICC criteria. A lower incidence of renal manifestation, less positivity for anti-dsDNA antibody, and a higher incidence of fever were observed in patients with N-com than in those with H-com. The occurrence of relapse and organ damage was not significantly different between patients with N-com and H-com. Conclusion Patients with N-com were less involved in renal manifestation and anti-dsDNA antibody positivity but had a higher incidence of fever than those with H-com, while having no disadvantage in SLE classification processes. Serum complement levels at the initial diagnosis of SLE may not predict prognosis