Mutation of KCNJ8 in a patient with Cantú syndrome with unique vascular abnormalities – Support for the role of K(ATP) channels in this condition

KCNJ8 (NM_004982) encodes the pore forming subunit of one of the ATP-sensitive inwardly rectifying potassium (K_ATP) channels. KCNJ8 sequence variations are traditionally associated with J-wave syndromes, involving ventricular fibrillation and sudden cardiac death. Recently, the K_ATP gene ABCC9 (SUR2, NM_020297) has been associated with the multi-organ disorder Cantú syndrome or hypertrichotic osteochondrodysplasia (MIM 239850) (hypertrichosis, macrosomia, osteochondrodysplasia, and cardiomegaly). Here, we report on a patient with a de novo nonsynonymous KCNJ8 SNV (p.V65M) and Cantú syndrome, who tested negative for mutations in ABCC9. The genotype and multi-organ abnormalities of this patient are reviewed. A careful screening of the K_ATP genes should be performed in all individuals diagnosed with Cantú syndrome and no mutation in ABCC9.     

SARS-CoV-2-Specific and Functional Cytotoxic CD8 Cells in Primary Antibody Deficiency: Natural Infection and Response to Vaccine

Journal of Clinical Immunology - CD8 cytotoxic T cells (CTLs) play a critical role in the clearance of virally infected cells. SARS-CoV-2-specific CD8 T cells and functional CTLs in natural...     

Multidrug resistant tinea corporis/cruris: Response to voriconazole

The increasing worldwide resistance to terbinafine and older antifungal drugs, coupled with often erratic clinical responses to itraconazole, leaves dermatologists with limited options to deal with dermatophytic infections. Recalcitrant dermatophytoses has however, over past few years, become a significant public health issue, especially in India. In this context, we present a patient who failed four systemic antifungals sequentially and was subsequently cured with a 2 week course of voriconazole, an antifungal not routinely used for dermatophytoses as yet.     

CD8+ T cells are crucial for humoral immunity establishment by SA14-14-2 live attenuated Japanese encephalitis vaccine in mice

The live attenuated SA14-14-2 Japanese encephalitis (JE) vaccine is a historical vaccine that protects against JE. Despite its extensive use, the mechanism of protective immunity conferred by the SA14-14-2 vaccine is not well established. Here, we used mouse models to understand the mechanism of the development of humoral immunity against the vaccine. The vaccine induces robust GC responses within a week postimmunization. In lethal virus challenge, we show that CD4⁺ T cells alone, but not CD8⁺ T cells, are sufficient to confer vaccine-mediated protection. However, the CD4-mediated protection was potentiated in the presence of vaccine-primed CD8⁺ T cells. Employing CD8-deficient mice, we show that both the protective traits of CD4⁺ T cells and the quality of antibody response to the vaccine are impaired in absence of CD8⁺ T cells. We further demonstrate that the poor protective immune response induced by the vaccine in absence of CD8⁺ T cells is mainly due to the impaired differentiation and function of follicular Th cells, leading to suboptimal GC reaction. Our study highlights an unprecedented role of CD8⁺ T cells in the establishment of humoral responses to the vaccine. By elucidating underlying cellular determinants of vaccine-induced protective immunity, our work has implications for rational design of vaccines against JE virus and related flaviviruses.     

Expression of VP1 protein of serotype A and O of foot-and-mouth disease virus in transgenic sunnhemp plants and its immunogenicity for guinea pigs

Recently, transgenic plants expressing immunogenic proteins of foot-and-mouth disease virus (FMDV) have been used as oral or parenteral vaccines against foot-and-mouth disease (FMD). They exhibit advantages like cost effectiveness, absence of processing, thermostability, and easy oral application. FMDV VP1 protein of single serotype has been mostly used as immunogen. Here we report the development of a?bivalent vaccine with tandem-linked VP1 proteins of two serotypes, A?and O, present in transgenic forage crop Crotalaria juncea. The expression of the bivalent protein in the transgenic plants was confirmed by Western blot analysis. Guinea pig reacted to orally or parenterally applied vaccine by humoral as well as cell-mediated immune responses including serum antibodies and stimulated lymphocytes, respectively. The vaccine protected the animals against a?challenge with the virus of serotype A?as well as O. This is the first report on the development of a?bivalent FMD vaccine using a?forage crop. Keywords: foot-and-mouth disease; sunnhemp; Agrobacterium tumefaciens; FMDV-VP1 gene; serotype O?and A; in planta transformation; transgenic plants; bivalent vaccine.     

A twin study of sex differences in social support

BACKGROUND: Social support may reduce the risk of psychiatric illness. Though perceived as an environmental measure, genetic factors may influence levels of social support. A relationship between social roles and personality with social support suggests possible sex effects on the sources of individual differences in social support. METHOD: We used the responses of MZ and DZ same and opposite sex twins to 16 questions regarding their social life. Six factors--friend support, relative support, friend problem, relative problem, confidants and social integration were used for structural equation modelling. Factor derived scales were analysed for genetic, shared and unique environmental influences. Quantitative and qualitative gender differences were analysed using the software package Mx. RESULTS: Except for relative support and confidants, no qualitative sex differences were seen. Genetic and individual specific environmental influences accounted for the variance for friend support, friend problems, relative problems and social integration and no quantitative gender differences were seen. For relative support genetic factors were detected in females but not males, while for confidants, the shared environment was important in females but not males. CONCLUSIONS: Except for relative support in males, genetic factors influence variation in all dimensions of social support. Shared environmental factors influence relative support and relative problems in both sexes. Sex differences were detected for confidants and relative support.     

Associations of killer cell immunoglobulin like receptors with rheumatoid arthritis among North Indian population

Introduction

Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disease of unknown etiology. Killer cell immunoglobulin-like receptors (KIR) expressed on surface of natural killer cells and CD28 null T-cells which are present in synovial membrane of RA. The present study has evaluated associations of KIR genes with RA among North Indian population from Uttar Pradesh.

Materials and methods

KIR genotypes were determined in 100 RA cases and 100 healthy controls using sequence specific primer polymerase chain reaction (PCR-SSP) method.

Results

RA cases positive for KIR3DS1 (OR = 1.17, p-value = 0.0498) and KIR2DS2 (OR = 2.21, p-value = 0.0120) showed risk associations. While, KIR2DL2 (OR = 0.40, p-value = 0.0026), KIR2DL3 (OR = 0.44, p-value = 0.0283) and KIR3DL1 (OR = 0.32, p-value = 0.0012) showed protective associations. Increased incidence of BB genotype (45%) was revealed among cases. Risk association was noted against telomeric region (OR = 2.12, p = 0.0120) genes for RA. Pair-wise linkage disequilibrium (LD) analysis among RA cases revealed KIR2DS1-2DL1 (D′ = 0.83, r² = 0.36), KIR3DL1-3DS1 (D′ = 1, r² = 0.58) and KIR2DL1-2DL2 (D′ = 1, r² = 0.61) to be in significant LD. KIR3DS1 and KIR2DS3 genes showed significant risk associations among RA patients with extra-articular manifestations (OR = 5.14, p-value = 0.0018; OR = 3.79, p-value = 0.0106) and in limited range of motion in affected joints (OR = 14.91, p-value = 0.0001; OR = 2.95, p-value = 0.0126).

Conclusion

The KIR activating genes have risk association with RA in the present study.