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Biomedical subjects

N Talal

Publications and source records attributed to N Talal.

At least 55 records · Page 3Linked to original sources
PubMed1993

Lymphoproliferation in primary Sjögren's syndrome. Evidence of selective expansion of a B cell subset characterized by the expression of cross-reactive idiotypes.

OBJECTIVE: To evaluate the possibility that lymphoproliferation in primary Sjögren's syndrome (SS) arises within a subset of B cells. METHODS: A panel of monoclonal antibodies (MAb) specific for rheumatoid factor (RF)-associated cross-reactive idiotypes (CRI) and anti-V kappa and anti-VH subgroup antibodies were used to define the clonality of B lymphocytes undergoing neoplastic transformation in 5 patients with primary SS. Anti-CRI antibodies were also used to study longitudinal variations in serum paraprotein levels and in vitro regulation of IgM and IgM-RF production by peripheral blood lymphocytes. The levels of CRI, IgM, and IgM-RF were quantitated in serum and culture supernatants by enzyme-linked immunosorbent assay. Heavy and light chain isotypes and VH subgroups of the paraproteins were determined by immunoelectrophoresis, immunofixation, and Western blotting. RESULTS: Paraproteins from all patients expressed an epitope associated with V kappa IIIb sub-subgroup of light chains. Three of the paraproteins were cryoglobulins with RF activity, all of which expressed the V kappa IIIb-associated CRI (detected by MAb 17-109) and the VHI-associated CRI (detected by MAb G6 and G8). None of the paraproteins expressed the VHIII-associated CRI (detected by MAb B6 and D12). The CRI were consistently expressed over a period of 5-6 years. The anti-CRI and anti-subgroup antibodies substantially inhibited spontaneous production of IgM-RF and IgM by peripheral blood B lymphocytes from 3 of the SS patients. CONCLUSION: These results suggest that lymphoproliferation in primary SS is highly selective, and that the anti-CRI antibodies can be used as an aid to early diagnosis as well as for monitoring and modulating the lymphoproliferative process in primary SS.

Adult↗
PubMed1993

Cloning of a human IgM autoantibody bearing a cross-reactive idiotype in a lambda expression vector: a new approach to studying autoantibodies.

The monoclonal antibody 4B4 is a human IgM,kappa which expresses a cross-reactive lupus-associated idiotype and has anti-Sm binding activity. We find that the VL nucleotide sequence of 4B4, like the 4B4 VH region, is encoded by unmutated germline genes. The 4B4 VH and VL were cloned into the ImmunoZap lambda expression vector to produce three recombinant immunoglobulin polypeptides. These recombinant polypeptides expressed, respectively, either the 4B4 VH or VL alone or a VH/VL heterodimer. ELISA showed that the VH/VL heterodimer retained anti-Sm antibody activity. The 4B4 idiotype was found predominantly on the VH. This report describes: (i) a method for producing recombinant immunoglobulin molecules from an IgM-secreting B cell line and (ii) the ability of recombinant antibody fragments expressed in Escherichia coli to retain the structural and antigenic properties of the native molecule.

Amino Acid Sequence↗
PubMed1993

Characterization of a cross-reactive idiotype on two human autoantibodies associated with systemic autoimmune disease.

A human-human hybridoma was derived from a patient with primary Sjogren's Syndrome. The monoclonal antibody from this hybridoma, P36, was found to be polyreactive. P36 shared idiotypic cross-reactivity with a lupus-associated monoclonal antibody called 4B4. There was a strong correlation between P36 and 4B4 idiotype levels in systemic lupus erythematosus sera. Western blot studies showed that this shared idiotype was found on the heavy chain of both antibodies. This study shows that the heavy chain is important in the expression of this idiotype and provides another immunologic link between these two rheumatic diseases.

Antibodies, Monoclonal↗
PubMed1993

Retroviruses, apoptosis and autogenes.

Autoimmunity and autoimmune disease are not the same. Autoimmunity is a normal consequence of aging, potentially reversible and possibly physiological. Autoimmune disease is dependent on genetic, viral, hormonal and psychoneuroimmunological factors. Aside from the apparently normal regulation of autoimmune responses by immune response genes, little is known about other genetic factors. Here, Norman Talal and John Mountz propose the term autogene to describe non-MHC genes which directly or indirectly interfere with important immunoregulatory actions. When mutated or otherwise genetically altered (e.g. by retrotransposon insertion), these genes predispose to immune dysregulation, lymphoproliferation and autoimmunity.

Animals↗
PubMed1993

Is central nervous system involvement a systemic manifestation of primary Sjögren's syndrome?

Central nervous system involvement in primary Sjögren's syndrome (pSS) is a controversial issue. Without an international criteria for the diagnosis of pSS, each research center must establish, publish, and strictly adhere to their own criteria. Therefore, patients should be made aware of professional uncertainties, particularly when therapeutic decisions are involved.

Central Nervous System Diseases↗
PubMed1993

Human kappa chain expression in a lambda phage vector: methods of isolating amplified cDNA affects cloning efficiency.

Three common methods of isolating amplified DNA were evaluated for their effects on cloning efficiency in a phage vector designed to express human kappa chain. The "glass milk" technique gave higher cloning efficiency and protein expression than phenol-chloroform extraction or microfiltration. This shows that the quality of amplified cDNA should be considered when studying the human antibody repertoire using this vector system.

Bacteriophage lambda↗
PubMed1993

Delayed type hypersensitivity in patients with rheumatoid arthritis.

Our study examines the relationship between in vivo delayed type hypersensitivity (DTH) and clinical and laboratory variables associated with rheumatoid arthritis (RA). Eleven patients with RA were examined. They were receiving no disease modifying drugs, immunosuppressive agents or corticosteroids. Skin tests were performed with the Multitest CMI system employing 7 antigens simultaneously. No patients were truly anergic, however, 3 of the 11 patients were hyporesponsive. No difference was noted between the total in vivo DTH responses of the patient and control populations. A significant correlation was observed between total DTH and the overall activity of the RA as measured by the erythrocyte sedimentation rate (ESR). However, there was no relationship between the total DTH scores and the degree of synovitis. There was no correlation between DTH and a variety of laboratory variables including the autologous mixed lymphocyte response, and the percentage of activated CD4+ or CD8+ T lymphocytes. These observations indicate that while anergy was uncommon in our population of patients with RA, decreased DTH responses were associated with greater disease activity as determined by the ESR.

Adult↗
PubMed1992

Signal transduction in Sjögren's syndrome T cells. Abnormalities associated with a newly described human A-type retrovirus.

OBJECTIVE: To study the effects of a novel A-type retrovirus, detected in cocultures of lip biopsy specimens from Sjögren's syndrome (SS) patients and a human T cell line, on the infected T cells. METHODS: Interleukin-2 (IL-2) and IL-6 secretion were measured by bioassay and enzyme-linked immunosorbent assay, respectively, in the infected and noninfected cell lines. Surface antigen expression was determined by flow cytometry, using monoclonal antibodies. Protein kinase C (PKC) activity was measured using an enzyme assay kit, and calcium mobilization was assessed with a fluorescent probe. RESULTS: Infected cells expressed less CD4 and IL-6 receptor, but more HLA-DR, compared with noninfected cells. Infected cells also produced less IL-2 and displayed reduced PKC activation and calcium mobilization. A similar defect in calcium mobilization was detected in T cells from SS patients. CONCLUSION: These data suggest a possible involvement of the newly described retrovirus in T cell abnormalities.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1992

Lymphoma in Sjogren's syndrome.

Sjogren's syndrome is an autoimmune disease with a known predisposition for lymphoma development. Eight of 120 patients with primary Sjogren's syndrome followed at the University of Ioannina over the past 7 years developed non-Hodgkin's lymphoma diagnosed according to the Kiel classification. The lymphomas differed by location and grading. Six were called low grade (immunocytoma) and two intermediate grade non-Hodgkin's lymphomas. Five of the immunocytomas involved the minor salivary or lacrimal glands. Immunoperoxidase staining for light chains revealed monoclonal populations. Two patients showed spontaneous regression not previously reported in Sjogren's syndrome. Thus, in Sjogren's syndrome, low grade non-Hodgkin's lymphomas and especially immunocytomas are the most common lymphomas. These lymphomas tend to evolve very slowly and may regress spontaneously. Given these facts, a conservative approach to treatment is indicated in those patients with only localized disease.

Adult↗
PubMed1992

The clinical effects of electrostimulation on salivary function of Sjögren's syndrome patients. A placebo controlled study.

A multi-center double-blind study of an electro-stimulator device was conducted to evaluate its ability to increase the production of saliva and reduce clinical symptomatology. A total of 77 Sjögren's syndrome patients at three centers were assigned to active devices (n = 40) or to placebo devices (n = 37). There were 2 male and 32 female patients assigned to active devices, and 1 male and 36 female patients assigned to placebo devices. The age range with the greatest number of patients was 60-69 years making up more than 31% of the study population. The selection criteria required the patients to have no greater than 0.2 g/min of whole salivary production (approximately 19% of normal salivary production). At the start of the study, the patients assigned the active device had a mean salivary production of 0.06 ml per min (6% of normal) and patients assigned placebo devices had a mean salivary production of 0.07 ml per min (7% of normal). There were three scheduled visits, 2 weeks apart, over a treatment period of 4 weeks. At all visits, the patients using active devices showed a statistically greater (P = 0.005 to 0.02) increase in the production of saliva than placebo patients. The study also evaluated the reduction of patients symptoms associated with xerostomia. Patients showed significant improvement in (1) difficulty in swallowing and (2) burning tongue (P = 0.008). Some patients on their initial visit had no response to the active device and did not show a significant response at subsequent visits.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Cross-reactivity of the B/B' subunit of the Sm ribonucleoprotein autoantigen with proline-rich polypeptides.

Using recombinant fusion proteins representing different regions of the human Sm B/B' polypeptide, the 4B4 monoclonal anti-Sm antibody was found to bind a C-terminus epitope that is proline-rich. 4B4 cross-reacted with the p24 gag protein of HIV-1 and with other polypeptides rich in proline residues, including collagen. BALB/c mice immunized with human collagen not only produced antibodies to the immunizing antigen but also antibodies to Sm. This immune mouse serum also recognized C-terminus B/B' fusion proteins. These data suggest that the Sm B/B' antigen contains a poly-Pro epitope that is shared by several autoantigens and retroviral proteins. These sites may be important in the induction of autoantibodies through molecular mimicry.

Animals↗
PubMed1992

Are endogenous retroviruses involved in human autoimmune disease?

A role for viruses in the etiopathogenesis of human autoimmune diseases has long been suspected but has not yet been proven. In Sjögren's syndrome (SS), there is continuing experimental support for the possible involvement of Epstein-Barr virus. Since the advent of AIDS, there is also great interest in retroviruses and autoimmune disease. We previously reported that 30% of SS patients and 36% of systemic lupus erythematosus (SLE) patients have serum antibodies to the p24 gag protein of HIV-1. We now report that two mechanisms classic for retroviruses (molecular mimicry and immunosuppression) may be operative in SS and SLE. The p24 gag protein shares a proline-rich epitope with the Sm nucleoprotein to which many SLE patients have antibodies. The impaired lymphocyte activation seen in peripheral blood T cells in SS patients is also seen in a human T cell line infected with an A-type retroviral particle linked to SS. Many studies suggest that endogenous retroviral sequences are important in immunoregulation. We now suggest that endogenous retroviral sequences may also be important in the etiology and pathogenesis of SS and SLE.

Autoantigens↗
PubMed1992

Regulation of IL-2 production by mononuclear cells from rheumatoid arthritis synovial fluids.

Products of polyamine oxidation down-regulate IL-2 production by peripheral blood T cells. We show here that the production of IL-2 by rheumatoid arthritis synovial fluid mononuclear cells is inversely correlated with the concentrations of polyamines in these cells. In addition, the inhibition of polyamine biosynthesis or oxidation in cultures of these cells enhances their ability to produce IL-2. Our findings suggest that polyamine oxidation plays an important role in the suppression of T cell function characteristic of rheumatoid arthritis synovial fluids.

Arthritis, Rheumatoid↗