Role of altered IL-33/ST2 immune axis in the immunobiology of Guillain-Barré syndrome.

BACKGROUND: The IL-33/ST2 immune axis plays crucial roles in infection and immunity. A dysregulated IL-33/ST2 axis can induce autoimmune reaction and inflammatory responses. Guillain-Barré syndrome (GBS) is an acute peripheral neuropathy, mostly caused by post-infection autoimmunity. The role of IL-33/ST2 axis is not known in GBS. This study aimed to explore the role of IL-33/ST2 axis in GBS. METHODS: Three single nucleotide polymorphisms (SNPs) of Il33 gene (rs16924159, rs7044343, rs1342336) and three SNPs of Il1rl1 gene (rs10192157, rs1041973, rs10206753) coding for suppressor of tumorigenicity 2 (ST2) were genotyped in 179 GBS patients and 186 healthy controls by TaqMan Allelic Discrimination Assay. Plasma levels of IL-33 and sST2 were measured in a subset of GBS patients (n = 80) and healthy controls (n = 80) by ELISA. RESULTS: The frequencies of CC genotype of rs10192157 (p = 0.043) and TT genotype of rs10206753 (p = 0.036) SNPs of Il1rl1 gene differed significantly between GBS patients and healthy controls. Gene-gene interaction between Il33 and Il1rl1 genes also conferred significant risk for GBS. In addition, the plasma sST2 levels were significantly elevated in GBS patients compared to healthy subjects (24,934.31 ± 1.81 pg/ml vs. 12,518.97 ± 1.51 pg/ml, p < 0.001). Plasma sST2 levels showed a significant correlation with the disability scores at the peak of neurological deficit in GBS patients. CONCLUSIONS: The IL-33/ST2 axis is suggested to influence the immunopathogenesis of GBS. Genetic variants of Il1rl1 gene might serve as a risk determinant of GBS and plasma sST2 levels might emerge as a biomarker of severity of GBS, if replicated further by other studies.

Case Report: Chronic Fungal Meningitis Masquerading as Tubercular Meningitis.

Phaeohyphomycosis causes a wide spectrum of systemic manifestations and can affect even the immunocompetent hosts. Involvement of the central nervous system is rare. A 48-year-old farmer presented with chronic headache, fever, and impaired vision and hearing. Serial MRIs of the brain showed enhancing exudates in the basal cisterns, and lesions in the sella and perichiasmatic and cerebellopontine angle regions along with enhancement of the cranial nerves and leptomeninges. Cerebrospinal fluid (CSF) showed lymphocytic pleocytosis with elevated protein and decreased glucose on multiple occasions. Clinical, imaging, and CSF abnormalities persisted despite treatment with antitubercular drugs and steroids for 2 years. Biopsy of the dura mater at the cervicomedullary junction revealed necrotizing granulomatous lesions, neutrophilic abscesses, and giant cells containing slender, pauci-septate, pigmented fungal hyphae. Fungal culture showed growth of Fonsecaea pedrosoi, which is classically known to cause brain abscesses. Here, we report the diagnostic odyssey in a patient with chronic meningitis from a region endemic for tuberculosis and describe the challenges in establishing the accurate diagnosis. Lack of therapeutic response to an adequate trial of empirical antitubercular therapy warrants search for alternative causes, including fungal meningitis. We highlight the uncommon manifestation of F. pedrosoi with chronic meningitis as well as the protracted clinical course despite not receiving antifungal therapy.