Biomedical subjects

N Nagarwalla

Publications and source records attributed to N Nagarwalla.

7 recordsLinked to original sources

PubMed1998

Oral pemphigoid. Subset of cicatricial pemphigoid?

OBJECTIVE: Cicatricial pemphigoid (CP) is an autoimmune blistering disease characterized by anti-basement membrane zone (BMZ) antibodies with a varied heterogeneous clinical spectrum. We sought to characterize a subset of patients with disease limited to the oral cavity. STUDY DESIGN: Twenty-nine random patients with vesiculobullous disease limited to the oral cavity were studied. We identified patients by clinical criteria, the presence of subepidermal/subepithelial bullae on routine histopathologic study, and deposition of IgG, complement, or both on the BMZ of perilesional tissue by immunopathological studies. Treatment included local and systemic therapies. Patients were monitored for a mean period of 6.7 years (range, 3.5 to 11 years). RESULTS: The female/male ratio was 4.8:1. Patients with limited or minimal disease received local therapy only. In patients with extensive or severe disease, the use of dapsone yielded significant clinical improvement. Long-term follow-up showed that patients with severe disease treated with dapsone followed a clinical course similar to that in patients with minimal disease. CONCLUSIONS: Oral pemphigoid is a distinct clinical subset of CP. Overall it has a relatively benign course compared with that in patients with CP involving the oral cavity and other mucosae and the skin. Patients with minimal disease respond satisfactorily to topical therapy. Patients with severe and extensive disease benefit from dapsone therapy. In most patients the clinical course is prolonged and treatment is required for several months; in our study the mean treatment period was 42 months (range, 24 to 78 months). All the patients in this study went into clinical remission and remained in remission on cessation of therapy. No other mucosae or the skin were involved during the follow-up period.

Adult↗

PubMed1998

Use of recombinant pemphigus vulgaris antigen in development of ELISA and IB assays to detect pemphigus vulgaris autoantibodies.

AIM/OBJECTIVE: The objectives of this study are: (1) to measure the titers of pemphigus vulgaris (PV) autoantibody in the sera of patients with active disease, using three different assays: (a) Indirect immunofluorescence (IIF) using monkey esophagus as a substrate, (b) immunoblot (IB) and, (c) enzyme-linked immunosorbent assay (ELISA) using recombinant PV antigen (rPVA). (2) To compare the sensitivity of these three assays. BACKGROUND: The titer of PV autoantibodies and disease severity and extent do not always correlate. This could be due to the lack of consistency and specificity of the substrate. Different results are obtained using different substrates. A standard substrate with uniformly controlled source of antigen would be more useful and clinically beneficial. METHODS: In this study we studied 25 PV patients, six each with bullous pemphigoid (BP), ocular cicatricial pemphigoid (OCP), mucous membrane pemphigoid (MMP), and herpes gestationis (HG), and sera from 16 normal subjects. IIF was used to determine the PV autoantibody using monkey esophagus. IB assay was used according to standard protocol using normal human epidermis and rPVA as substrates. ELISA was performed using rPVA as antigens expressed in E. coli. RESULTS: Sera of all 25 PV patients showed binding to the rPVA, normal human sera and the sera from the six BP, six OCP, six MMP, and six HG patients did not show any binding. In addition, we used antisera from rabbits immunized with PVA peptides (Bos-1, Bos-6) which also showed binding to rPVA, whereas normal rabbit sera did not show any reactivity. ELISA and IB titers in all the patients were 2.5 to 160 times higher than with the conventionally used IIF assay. The titers of the PV specific autoantibody measured using the rPVA did not show statistically significant differences between the ELISA and IB assays. CONCLUSIONS: IB and ELISA are superior to IIF in evaluating the antibody levels in PV patients. ELISA is more practical and is preferable to IB and is recommended for clinical use.

Animals↗

PubMed1995

Correlation of peptide specificity and IgG subclass with pathogenic and nonpathogenic autoantibodies in pemphigus vulgaris: a model for autoimmunity.

Pemphigus vulgaris (PV) is a rare, potentially fatal, autoimmune disease that affects the skin and mucous membranes. The PV antigen (PVA) has been characterized as desmoglein 3. PV patients carry HLA-DR4- or HLA-DR6-bearing extended haplotypes. We recently demonstrated that patients with active disease have high titers of PV autoantibodies of the IgG1 and IgG4 subclasses. Patients in remission, healthy unaffected relatives, and some MHC-matched normal individuals have low levels of PV autoantibodies, which are IgG1 only. Furthermore, intraperitoneal injection of IgG from patients with active disease caused clinical disease in mice, but IgG from patients in remission, healthy relatives, or MHC-matched normal individuals did not. We prepared 12 peptides of 30 amino acids each (peptides Bos 1-12) spanning the extracellular domain of PVA. Patients with active disease recognize peptides Bos 1 and Bos 6 with high titers of IgG1 and IgG4 autoantibodies. Patients in remission have IgG1 autoantibodies to peptide Bos 1 only, in statistically significantly lower titers (P < 0.01). They no longer have IgG4 subclass autoantibodies to peptide Bos 6. Healthy relatives and normal unrelated individuals have low levels of only IgG1 autoantibodies that recognize only Bos 1. In vitro studies indicate that Bos 6-specific IgG and, to a lesser extent, Bos 1-specific IgG can cause acantholysis. Our data suggest that Bos 6-specific IgG4 is probably the main acantholytic autoantibody, while Bos 1-specific IgG4 may act as a facilitator or enhancer of the process. In this study we illustrate some of the paradigms that demonstrate the interactions between the MHC, subclass of autoantibodies, and peptide specificities of the autoantibodies in the autoimmune process. Thus, PV provides an important model to study the pathogenesis of autoimmunity.

Amino Acid Sequence↗

PubMed1995

Spatial disease clusters: detection and inference.

We present a new method of detection and inference for spatial clusters of a disease. To avoid ad hoc procedures to test for clustering, we have a clearly defined alternative hypothesis and our test statistic is based on the likelihood ratio. The proposed test can detect clusters of any size, located anywhere in the study region. It is not restricted to clusters that conform to predefined administrative or political borders. The test can be used for spatially aggregated data as well as when exact geographic co-ordinates are known for each individual. We illustrate the method on a data set describing the occurrence of leukaemia in Upstate New York.

Cluster Analysis↗

PubMed1995

Antibodies to the 70-kDa heat-shock protein in patients with thermal burns.

Autoantibodies in the sera of patients with thermal burns, which bind to a protein in the intercellular substance of the epidermis, have been previously described. By immunoblot analysis, we have shown that a 68-kDa epidermal protein is the predominant antigen to which these autoantibodies bind. Our study also demonstrates that this 68-kDa epidermal protein is similar to the bovine brain 70-kDa heat-shock protein (hsp 70). In addition, we have detected significantly elevated levels of IgG antibodies to the bovine brain hsp 70 in all of the sera from random burned patients (n = 33), in comparison with the levels in the sera of normal, healthy controls (n = 43, P < 0.0001). The precise role and significance of these autoantibodies and their influence on the immune system in burned patients remain to be determined.

Animals↗

PubMedDate not supplied

Childhood leukaemia in Sweden: using GIS and a spatial scan statistic for cluster detection.

The study of disease clustering is becoming increasingly common in the field of medical epidemiology. There is great public concern and numerous reports on perceived clusters of various diseases, and with cancers, and especially leukaemia, being the most commonly studied. We present a population based study on acute childhood leukaemia in Sweden 1973-1993, illustrating the possibility of a system for full-scale spatial epidemiological study design. The aim of the study is to test a large set of childhood leukaemia cases for the presence of geographical clusters. Necessary prerequisites, in the form of extensive population and disease data, a tool for geographical spatial analysis and a proper statistical method were fulfilled. No significant clusters were found.

Acute Disease↗

PubMedDate not supplied

A scan statistic with a variable window.

Given N points or events occurring according to some probability distribution in the unit interval (0, 1), the simple scan statistic is defined to be the maximum number of points in any sub-interval of length d. In many areas, as in epidemiology, it is used to test the null hypothesis that the events are random, against the alternative that they cluster within some window of fixed width d. Since d must be chosen without snooping at the data, the test restricts the alternative to clusters of a fixed size. In this paper, we propose a scan statistic with a variable window, whose size does not need to be chosen a priori. This test is the generalized likelihood ratio test for a uniform null distribution against an alternative of non-random clustering which allows for clusters of variable width. A simple algorithm for the implementation of the method is given and applied to birth defects data previously analysed by a simple scan statistic.

Algorithms↗