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Biomedical subjects

Harvinder S Luthra

Publications and source records attributed to Harvinder S Luthra.

9 recordsLinked to original sources
PubMed2005

Requirement for CD28 may not be absolute for collagen-induced arthritis: study with HLA-DQ8 transgenic mice.

CD28 is required to achieve optimal T cell activation to an Ag. To determine the role CD28 costimulation plays in collagen-induced arthritis, we have generated DQ8 transgenic, CD28-deficient mice. DQ8 mice deficient for CD28 had comparable numbers of CD4 and CD8 T cells as DQ8.CD28(+/+) mice. DQ8.CD28(-/-) mice develop collagen-induced arthritis with delayed onset and less severity than DQ8.CD28(+/+) mice. T cells from DQ8.CD28(-/-) mice did not respond to type II collagen efficiently in vitro, although the response to DQ8-restricted peptides was similar to that in the parent mice. There was no functional defect in T cells as observed by proliferation with Con A. Cytokine analysis from in vitro study showed the production of high levels of the inflammatory cytokine, IFN-gamma, in response to type II collagen. We observed an increase in CD4(+)CD28(-)NKG2D(+) cells after immunization, suggesting an important role for cells bearing this receptor in the disease process. CD28(-/-) mice also have an increased number of DX5(+) cells compared with CD28(+/+) mice, which can lead to the production of high levels of IFN-gamma. DQ8.CD28(-/-) mice had an increased number of cells bearing other costimulatory markers. Cells from DQ8.CD28(-/-) mice exhibited a lower proliferation rate and were resistant to activation-induced cell death compared with DQ8.CD28(+/+) mice. This study supports the idea that CD28 plays a crucial role in the regulation of arthritis. However, in the absence of CD28 signaling, other costimulatory molecules can lead to the development of disease, thus indicating that the requirement for CD28 may not be absolute in the development of arthritis.

Animals↗
PubMed2005

An unusual presentation of rheumatoid meningitis.

BACKGROUND: Central nervous system involvement in rheumatoid arthritis can rarely occur in the absence of systemic disease. Rheumatoid meningitis has not been reported to present as spells of neurologic dysfunction. PATIENT AND METHODS: The authors describe a woman with a history of well-controlled rheumatoid arthritis who presented with headaches and spells of focal neurological dysfunction. Brain magnetic resonance imaging, brain biopsy, and temporal artery biopsy were required to make the diagnosis of rheumatoid meningitis with arteritis. RESULTS: Neuroimaging revealed abnormal leptomeningeal enhancement. Necrotizing granulomatous inflammation was seen on meningeal and brain biopsy. A temporal artery biopsy showed evidence of arteritis without giant cells. CONCLUSIONS: The possibility of central nervous system involvement by rheumatoid arthritis should be considered in patients with a history of rheumatoid arthritis even in the absence of systemic symptoms. Making the diagnosis may require meningeal and brain biopsy. The condition may be steroid responsive.

Aged↗
PubMed2004

Relapsing polychondritis.

SUMMARY: Relapsing polychondritis is a unique, rare autoimmune disorder in which the cartilaginous tissues are the primary targets of destruction but the immune damage can spread to involve noncartilaginous tissues like the kidney, blood vessels, and so forth. The manifestations of the disease can take many different forms and the pathogenesis is still unclear. It may occur in a primary form or it may be associated with other disease states. This article summarizes important aspects of the disease with a focus on recent information regarding clinical manifestations, disease associations, pathogenesis, and advances in therapeutics.

Antirheumatic Agents↗
PubMed2004

Risk factors for methotrexate-induced abnormal laboratory monitoring results in patients with rheumatoid arthritis.

OBJECTIVE: To determine risk factors for methotrexate (MTX)-induced hepatic and hematologic laboratory abnormalities in patients with rheumatoid arthritis (RA). METHODS: Measurements of aspartate aminotransferase (AST), white blood cell counts, and platelet counts were collected in a database of patients with RA receiving MTX from 1991 through 2002. Potential risk factors for toxicity were recorded on each patient. RESULTS: Four hundred and eighty-one patients were followed for 2,323 person-years of MTX exposure. MTX was discontinued permanently because of abnormal laboratory test results in 22 patients (4.6%), the majority of whom (17/22, 77%) had elevated AST values. The body mass index (BMI) was significantly higher in those patients where MTX was permanently discontinued than in those in whom it was not (p < 0.03). Independent predictors of a significantly higher percentage of abnormal AST values were lack of folate supplementation (p < 0.001) and untreated hyperlipidemia (p < 0.02). Of the 17 patients in whom MTX was discontinued permanently because of an elevated AST value, 11/17 (65%) had either lack of folate supplementation or untreated hyperlipidemia. Hypoalbuminemia correlated independently with an increased percentage of abnormal platelet counts (p < 0.03). CONCLUSION: Lack of folate supplementation, untreated hyperlipidemia, and elevated BMI identified patients receiving MTX at risk for transaminase elevation, and low serum albumin was a risk factor for thrombocytopenia. Nonalcoholic fatty liver disease could be the underlying risk factor for transaminase elevation in patients with hyperlipidemia and obesity.

Adult↗
PubMed2003

Auricular chondritis in NOD.DQ8.Abetao (Ag7-/-) transgenic mice resembles human relapsing polychondritis.

Relapsing polychondritis is a multisystem autoimmune disease involving cartilage destruction but no known causative antigen. HLA-DQ8 has been associated with various autoimmune diseases in humans. To study the role of DQ8 in autoimmune diseases, we have generated transgenic mice expressing DQ8 (DQA1*0301, DQB1*0302) in a NOD background lacking endogenous class II molecules (Abetao). Upon immunization with type II collagen (CII), 85% of NOD.DQ8 mice develop severe experimental polychondritis, auricular chondritis, and polyarthritis, with clinical and histological similarities to relapsing polychondritis (RP) in humans. CII-immunized mice mount a T cell response and produce Ab's to type IX collagen (CIX) and self-CII. Transgene-negative littermates do not develop any serological and clinical manifestations following immunization. B10.DQ8 transgenic mice develop polyarthritis and Ab's to CII only. The susceptibility to auricular chondritis in NOD.DQ8 mice can be attributed to response to CIX. A higher number of activated cells, CD4+CD44(hi)CD62L(lo), and lower regulatory cells CD4+CD152+CD25+ were observed in NOD.DQ8 mice compared with B10.DQ8 mice. The NOD.DQ8 mice provide a model of RP with a high disease incidence and multiple organ involvement to investigate putative autoantigen and regulatory cells involved in disease pathogenesis. An experimental model restricted by the human class II molecule will be valuable when studying the role of various collagens in immunologic and pathologic responses in human RP.

Animals↗
PubMed2002

Determinants of patient satisfaction in chronic illness.

OBJECTIVE: To determine whether primary care provided by generalists versus subspecialists resulted in different levels of patient satisfaction among persons with chronic illness. METHODS: A survey containing the Primary Care Provider Questionnaire and the Health Status Questionnaire (HSQ) was mailed to 2 population-based cohorts of patients with rheumatoid arthritis (RA) or diabetes mellitus (DM). All subjects were at least 35 years old and Rochester, Minnesota residents. Descriptive statistics, Spearman correlation coefficients, and multiple regression models were used to describe and compare the determinants of patient satisfaction. RESULTS: A total of 86 people (74% female) with RA and 208 people (56% male) with DM responded to the survey. Age range was 41-95 years and median disease duration was 8.7 years (RA) and 13.0 years (DM). Most patients described their health as fair or good. After adjusting for sex differences, RA patients were more likely than DM patients to report having a specialist as their primary care doctor. RA patients, whether reporting seeing a specialist or a generalist, had comparable HSQ physical health, mental health, social functioning, vitality, and bodily pain scores. DM patients seeing a specialist had more bodily pain and poorer physical functioning than those seeing a generalist. Across both chronic illnesses and physician specialties, median scores for patient satisfaction ranged from 17-18 for overall satisfaction (maximum 20); 30-33 for interpersonal skills (maximum 35); 23-26 for technical quality (maximum 30); and 20 for access to care (maximum 25). Multiple linear regression models revealed that 6.8-7.3% of the variation in satisfaction could be explained by HSQ scores, patient demographics, and physician specialty. CONCLUSION: Both RA and DM patients were highly satisfied with their care, regardless of the specialty of the provider. Physician specialty, patient demographics, and HSQ scores explained only a small proportion in the variation in satisfaction. These findings point to the need for additional research to further elucidate the determinants of patient satisfaction.

Adult↗
PubMed2002

HLA class II influences the immune response and antibody diversification to Ro60/Sjögren's syndrome-A: heightened antibody responses and epitope spreading in mice expressing HLA-DR molecules.

Abs to Ro/SSA Ags in the sera of patients with systemic lupus erythematosus and Sjögren's syndrome are influenced by the HLA class II genes. To investigate the role of individual HLA class II genes in immune responses to human Ro60 (hRo60), mice lacking murine class II molecules and carrying either HLA genes DR2(DRB1*1502), DR3(DRB1*0301), DQ6(DQA1*0103/DQB1*0601), or DQ8(DQA1*0301/DQB1*0302), were immunized with rhRo60. The results show that hRo60 induces strong T and B cell responses in DR2, DR3, and DQ8 mice in comparison to weaker responses in DQ6 mice. In all mice, the majority of the dominant T cell epitopes were located in the amino portion (aa 61-185) and the carboxy portion (aa 381-525) of the hRo60 molecules. In contrast, the early dominant B cell epitopes were located in the middle and carboxy portion of the hRo60 molecule (aa 281-315 and 401-538). In DR2, DR3, and DQ8 mice, the B cell epitopes subsequently spread to the amino and carboxy portion of the hRo60 molecule but were limited to the middle and carboxy portion in DQ6 mice. The DR2 and DR3 mice produced the highest titers of immunoprecipitating Abs against hRo60 and native mouse Ro60. In addition, only DR2 mice exclusively produced immunoprecipitating Abs to native mouse Ro52 and Abs to mouse La by slot blot analysis, whereas in other strains of mice Abs to mouse La were cross-reactive with the immunogen. The results of the present study demonstrate the importance of HLA class II in controlling the immune responses to the Ro-ribonucleoprotein.

Amino Acid Sequence↗