Biomedical subjects
N Talal
Publications and source records attributed to N Talal.
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.
Sjögren's syndrome and retroviral protein reactivity: reply.
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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.
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)
The third international symposium on Sjogren's syndrome.
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Psychoneuroimmunology. Commentary.
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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.
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.
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.
Evidence for possible retroviral involvement in autoimmune diseases.
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Systemic lupus erythematosus and Sjögren's syndrome.
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Sjögren's syndrome: historical overview and clinical spectrum of disease.
Sjögren's syndrome is a chronic autoimmune and inflammatory disease characterized by lymphocyte proliferation that progressively destroys exocrine glands. The lymphocytes can infiltrate other and more vital organs and may at times become malignant. Another name for this disease is autoimmune exocrinopathy. It was first described over 100 years ago both as a benign syndrome of oral and ocular dryness and also as a lymphoid malignancy. Thus, Sjögren's syndrome is related to the autoimmune rheumatic diseases, as well as to lymphoid B-cell malignancies.
AIDS and Sjogren's syndrome.
HIV infection can produce a clinical syndrome and immunologic changes similar to those seen in SS. HIV infection can occasionally result in an SS-like disease but without the formation of antibodies to Ro(SS-A) or La(SS-B). Could this mean that a retrovirus yet to be discovered is responsible for the autoimmune exocrinopathy known as SS? Evidence to date is circumstantial, based on antibodies to a retroviral protein (p24). The idea that retroviruses act in a genetically susceptible host to cause SS is a reasonable hypothesis. Syphilis and Lyme disease are both models where infectious organisms cause chronic multi-system disease. The virus of SS need not be a foreign invader but could be an endogenous retrovirus contained within our own genetic material (10, 11). More investigation is needed to exploit the research opportunities that have appeared in clinical immunology since the AIDS epidemic first appeared.
Anti-peptide antibodies detect a lupus-related interspecies idiotype that maps to H chain CDR2.
Antibodies to the small nucleoprotein Sm occur spontaneously in human and murine systemic lupus erythematosus. Human and mouse monoclonal anti-Sm autoantibodies designated 4B4 and Y2 share an idiotype (Id) determinant located on the Ig H chain. To understand the molecular basis of this cross-reactivity, the VH regions of both antibodies were sequenced and analyzed for homology. The antibodies showed only 49.6% homology. The second complementary determining region (CDR2) was the most likely candidate for the Id site. To investigate this possibility, rabbit antiserum was made against a peptide corresponding to the CDR2 of 4B4. This antiserum was specific for the immunizing peptide and reacted weakly to a peptide corresponding to the CDR2 of Y2. Anti-CDR2 antibody bound to 4B4 and Y2 but not to other human and mouse mAb. Binding was directed at the H chain when analyzed by Western blots. Anti-CDR2 antibody blocked anti-Id antibody binding to 4B4 and Y2 by 58% and 24%, respectively. These studies suggest that this interspecies Id maps to the H chain CDR2 and that a conserved Id can occur within molecules that are otherwise radically different.
Systemic lupus erythematosus, autoimmunity, sex and inheritance.
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An evaluation of salivary scintigraphy in Sjögren's syndrome.
Sequential salivary scintigraphy, labial salivary gland biopsy, and measurement of stimulated parotid flow rate were performed in 50 patients suspected of having Sjögren's syndrome. The value of these tests in the diagnosis of this disease was compared. Salivary scintigraphy and labial salivary gland biopsy can be used together to diagnose the oral component of Sjögren's syndrome. Abnormal salivary scintigraphy correlated with both of the other tests and may be considered optional in the diagnostic evaluation.
Immunoblastic sarcoma with features of Sjögren's syndrome and systemic lupus erythematosus in a patient with immunoblastic lymphadenopathy.
A patient with immunoblastic lymphadenopathy and features of Sjögren's syndrome and systemic lupus erythematosus is presented. Clinical features included generalized lymphadenopathy, rash, alopecia, and synovitis, with associated laboratory abnormalities of a positive antinuclear factor and double-stranded DNA antibodies, positive lupus band test, and hemolytic anemia. Symptoms of Sjögren's syndrome included dry eyes and mouth and swollen parotid gland; biopsy results of the accessory salivary glands were positive. At autopsy immunoblastic sarcoma was found that involved the myocardium, which stained for both kappa and lambda light chains by immunoperoxidase techniques.