Dominance and improved survivability of human γδT17 cell subset aggravates the immunopathogenesis of pemphigus vulgaris.

Human γδ T cells are highly enriched in epithelial cell-dominated compartments like skin. Nonetheless, their function in the pathogenesis of pemphigus vulgaris (PV), an autoimmune skin disorder, is lacking. Therefore, we investigated the functional expression of human γδT cell subsets along with their homing chemokine receptor-ligand and inflammatory cytokines in the immunopathogenesis of PV. Estimation of the frequency of γδT cell subsets by flow cytometry revealed four major subsets of γδ T cells (γδT1, γδT2, γδT17, γδTreg) in both control and PV circulation. The elevated frequency of γδT17 cells producing IL17 and expressing CCR6 receptor suggests their inflammatory and migratory potential in PV. In vitro culture of γδ T cells from patients showed increased mRNA expression of inflammatory cytokines IL17, RORγt, IL23, IL1, and co-stimulatory markers, CD27 and CD70. These findings correlated the role of IL1 and IL23 cytokines that alleviate the Th17 population in PV. Cytotoxic activities of γδ T cells were higher and inflammatory γδT17 cells were localized in the skin of PV whereas γδTreg cells associated TGFß and FOXP3 were lowered. Hyperinflammatory phenotype of the γδT17 cell subset and its migratory potential might be aiding in the pathogenesis of PV, whereas γδTreg cells fail to suppress these inflammatory responses. Hence, γδT17 cell-associated markers can be targeted for identifying novel therapeutics in PV.

Design and synthesis of multiple antigenic peptides and their application for dengue diagnosis.

Major difficulty in development of dengue diagnostics is availability of suitable antigens. To overcome this, we made an attempt to develop a peptide based diagnosis which offers significant advantage over other methods. With the help of in silico methods, two epitopes were selected from envelope protein and three from NS1 protein of dengue virus. These were synthesized in combination as three multiple antigenic peptides (MAPs). We have tested 157 dengue positive sera confirmed for NS1 antigen. MAP1 showed 96.81% sera positive for IgM and 68.15% positive for IgG. MAP2 detected 94.90% IgM and 59.23% IgG positive sera. MAP3 also detected 96.17% IgM and 59.87% IgG positive sera. To the best of our knowledge this is the first study describing the use of synthetic multiple antigenic peptides for the diagnosis of dengue infection. This study describes MAPs as a promising tool for the use in serodiagnosis of dengue.

Inter- and intra-observer variability in three grading systems for oral epithelial dysplasia.

BACKGROUND AND OBJECTIVES: Management of oral premalignant lesions depends on clinical assessment and grading of oral epithelial dysplasia (OED), which remains one of the most important predictors of malignant potential. Numerous grading systems for OED exists with varying sets of assessing criteria and are largely considered subjective. The present study attempted to assess the inter- and intra-observer variability in three grading systems: Binary system, WHO (2005) and Ljubljana systems. METHODOLOGY: Histopathological grading of 63 cases of leukoplakia was performed by two oral pathologists and one general pathologist, who were blinded, using all the three grading systems at different time intervals and was repeated twice. Inter- and intra-observer variability was then evaluated by multivariate kappa analysis. RESULTS: Inter-observer agreement in the two set of observations was found to be "slight" in WHO (k = 0.001 and 0.039), "slight" and "poor" in binary (k = 0.108 and -0.007), "poor" and "slight" in Ljubljana's (k = -0.027 and 0.106) grading systems. Intra-observer agreement ranged from "slight" to "fair" (k = 0.128 and 0.295) in WHO, "fair" to "moderate" (k = 0.224 and 0.420) in binary and "slight" to "fair" (k = 0.161 and -0.353) in Ljubljana's grading systems. CONCLUSIONS: The binary system of classification proved to have an overall better inter- and intra-observer agreement. This study also showed better intra-observer agreement in all the grading systems as well as in individual histopathological parameters. Defining the individual parameters more objectively with the reproducible structuring of the grading systems and training of the pathologists would help reduce the variability in diagnosing dysplasia.

Association of TNF-α-(308(GG)), IL-10(-819(TT)), IL-10(-1082(GG)) and IL-1R1(+1970(CC)) genotypes with the susceptibility and progression of leprosy in North Indian population.

Leprosy is an infectious disease caused by M. leprae. We analyzed 48 cytokine polymorphisms in 13 (pro as well as anti-inflammatory) cytokine genes using PCR-SSP assay in 102 leprosy patients and 120 healthy controls with intent to find out a link between cytokine polymorphisms and disease susceptibility. TNF-α (-308) GG, IL-10 (-819) TT, IL-10 (-1082) GG and IL1R (+1970) CC genotypes are found to be predominant (p=0.01, p=0.02, p=0.0001 and p=0.001, respectively) in both tuberculoid as well as lepromatous leprosy patients. This observation suggests these genotypes as play the central role(s) in the progression of disease. CBA assay demonstrates the varied serum concentration of these cytokines with respect to their genotypes. The above genotypes appeared as high producer genotypes in our study. Even in presence of high produce genotypes, TNF-α level are found to be affected/masked by the presence of IL-10 in leprosy patients. Expressional masking of TNF-α is associated with the expression of IL-10 in these patients. This is one the negative impact of SNP-SNP interaction in leprosy patients. Therefore, we can conclude that cytokine gene polymorphisms determine the predisposition to the leprosy progression.

Neutrophilic eccrine hidradenitis: a new culprit-carbamazepine.

Neutrophilic eccrine hidradenitis (NEH) is a distinctive dermatosis occurring in patients with malignancy or undergoing chemotherapy. This disorder is characterized by a neutrophilic infiltrate around the eccrine glands and secretory coils, and is associated with necrosis. It must be distinguished from infections, drug eruptions, malignancies or other forms of skin diseases. As it is a self-limiting condition, establishing the diagnosis will avoid unnecessary investigations and treatment. Here we report a case of NEH in a 40-year-old woman suspected to be due to carbamazepine.

Cervical thymic cyst: a case report.

Cervical thymic cysts are rare lesions often misdiagnosed clinically as branchial cyst. Here we report a rare case of multiloculated thymic cyst in a young 8 year old male child on the left side of the neck. Histopathology of the excised cyst revealed mural nodules of thymic tissue with prominent Hassal's corpuscles associated with multiloculated cyst. This case is presented here for its rarity. It should be included in the differential diagnosis of neck masses in children.

Primary cutaneous adenoid cystic carcinoma of the chest wall: a rare entity.

Primary Cutaneous Adenoid Cystic Carcinoma (PCACC) is a rare form of cutaneous carcinoma. It closely resembles adenoid cystic carcinoma of salivary glands. The lesion tends to infiltrate and recur locally but rarely metastasizes to distant organs and lymph nodes. We present here a case of a31-year-old male with complaints of swellings in the chest wall and scalp, progressively increasing in size over a period of 10 years. Clinical diagnosis of sebaceous cysts of scalp and chest wall was made. Histopathology revealed PCACC of the chest wall and dermoid cyst of the scalp.

Cytology of hyalinising trabecular adenoma-like variant of medullary thyroid carcinoma.

Medullary thyroid carcinoma is a rare thyroid neoplasm that can be either sporadic or familial. It occurs in adults, presenting as a solitary cold nodule on thyroid scan. Most are solid, firm, and non-encapsulated, and occur in the mid portion or upper half of the thyroid gland, corresponding to areas with greater numbers of C cells. We present a case of a 36-year-old female with a swelling in the front of her neck for six years. Fine needle aspiration done elsewhere revealed spindle cells, suggestive of a 'spindle cell neoplasm'. The histopathology of the thyroidectomy specimen showed features of a hyalinizing trabecular adenoma-like variant of medullary carcinoma. Subsequently, we performed aspiration on the received specimen and studied the cytological findings. The cytological diagnosis of this variant requires identification of the dual spindle and ovoid cell population and the granular neuroendocrine chromatin.

Multiloculated cervical thymic cyst.

In this study, we report a rare case of cervical thymic cyst in an 8-year-old child.

Inflammatory fibroid polyp of jejunum causing jejuno-jejunal intussusception.

Intussusceptions originating in the jejunum are rare. We report a 20-year-old woman who had a chronic jejuno-jejunal intussusception due to an inflammatory fibroid polyp manifesting in the post-partum period as peritonitis. Resection-anastomosis of the intussuscepted segment was done. She is well one year later.

Combined primary fibrosarcoma--malignant fibrous histiocytoma of the breast: a case report.

Malignant mesenchymal tumours of the breast are relatively rare tumours that have yet to receive universal approval in terms of terminology. With classification based on histogenesis rapidly gaining acceptance, we present a case with histological features of both fibrosarcoma and malignant fibrous histiocytoma, with the former predominating. An unusual finding was the presence of large areas with haemangiopericytomatous appearance. The literature on changing concepts regarding classification of malignant mesenchymal tumours of the breast is reviewed.