Norman Talal

Classification criteria for Sjögren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group

Classification criteria for Sjögrens syndrome (SS) were developed and validated between 1989 and 1996 by the European Study Group on Classification Criteria for SS, and broadly accepted. These have been re-examined by consensus group members, who have introduced some modifications, more clearly defined the rules for classifying patients with primary or secondary SS, and provided more precise exclusion criteria.

The histopathology of Sjögren's syndrome in labial salivary gland biopsies

Abstract Labial salivary gland biopsy specimens from seventy-five patients evaluated for Sjogrens syndrome were examined histologically. Clinically severe cases of Sjogrens syndrome showed the most marked histologic change. Focus score was found to be the most useful histologic index of severity of the disease. Large numbers of plasma cells were found in small foci and mild cases. Plasma cells were decreased in proportion, compared to lymphocytes, in larger foci and severe cases. These observations are discussed in the light of possible mechanisms of tissue damage in this disease.

The development of malignant lymphoma in the course of Sjögren's syndrome

Abstract Of fifty-eight patients with Sjogrens syndrome followed at the National Institute of Arthritis and Metabolic Diseases, reticulum cell sarcomas developed in three, and lesions resembling Waldenstroms macroglobulinemia in a fourth. These changes were present in lymph nodes and organs exclusive of the salivary and lacrimal glands. These patients have certain clinical and laboratory features in common which distinguish them from patients with the usual benign cases of Sjogrens syndrome. These features include a relatively high incidence of splenomegaly, purpura, vasculitis, leukopenia, lymphopenia and hypogammaglobulinemia. The gamma globulin abnormalities have been investigated by immunoelectrophoretic analysis, ultracentrifugation and fluorescent antibody technics. In one patient, gamma globulin decreased from elevated to markedly low levels; the rheumatoid factor and tissue antibodies disappeared as reticulum cell sarcoma developed. In another patient, lymph nodes were populated with an abnormally large proportion of cells containing 19S macroglobulin, and several cells exhibited unusual intranuclear inclusions which stained positive with periodic acid-Schiff stain. The relationship between connective tissue diseases, gamma globulin abnormalities, thymomas and malignant lymphomas is discussed. The hypothesis is presented that in Sjogrens syndrome the chronic state of immunologic hyperactivity and the proliferation of immunologically competent cells producing abnormal tissue antibodies predispose to the relatively frequent development of malignant lymphoma.

Measurement of serum DNA-binding activity in systemic lupus erythematosus.

Abstract Antibodies to DNA were demonstrated in the serums of patients with systemic lupus erythematosus (SLE) by ammonium sulfate precipitation. DNA is soluble in 50 per cent saturated ammonium sulfate, whereas immunoglobulins and immunoglobulin-bound DNA are insoluble. When ammonium sulfate is added to a mixture of radioactive DNA and serum, the precipitate contains radioactivity if DNA is bound to immunoglobulins. Abnormal binding was found in serum of 75 per cent of unselected patients with SLE, 25 per cent with Sjogrens syndrome, 5 per cent with related disease and 2 per cent of normal subjects. All of 52 selected SLE serums with positive, as well as 21 of 32 SLE serums with negative, complement-fixation tests for anti-DNA antibodies had abnormal binding. Binding activity was associated with immunoglobulin G of serum. High binding values were seen chiefly in patients with active SLE renal disease; marked reductions accompanied clinical improvement. The test overcomes problems inherent in other metho...

Evidence That the Malignant Lymphoma of Sjögren's Syndrome Is a Monoclonal B-Cell Neoplasm

We studied the malignant lymphomas that developed in patients with Sjögrens syndrome and the antecedent benign salivary-gland lesions to determine their cellular characteristics. We used an immunoperoxidase technic that identified intracellular gamma, alpha and mu heavy chains and kappa and lambda light chains. In six of nine patients, the lymphomas were composed of cells containing intracytoplasmic immunoglobulin that was exclusively IgMK. The benign lymphoepithelial salivary-gland lesions preceding these malignant tumors consisted of approximately equal numbers of lymphoid cells containing either kappa or lambda light chains. Thus, in some patients with Sjögrens syndrome, there may be a progression in the lympho-proliferative lesions from a polyclonal infiltrate to a monoclonal neoplasm. Intracytoplasmic immunoglobulin identifies six of the nine cases as being B-cell in origin.

Extrasalivary lymphoid abnormalities in Sjögren's syndrome (reticulum cell sarcoma, “pseudolymphoma,” macroglobulinemia)

Abstract Eight patients with Sjogrens syndrome and extrasalivary lymphoid abnormalities are described. In all eight lymphadenopathy or other lymphoid infiltrates were sufficient to arouse a clinical suspicion of lymphoma. Two have primary macroglobulinemia, one has reticulum cell sarcoma and five have a syndrome designated as pseudolymphoma. Four of the latter have significant elevations of serum IgM macroglobulins. Histologically, the salivary gland lesions in these patients are indistinguishable from those in other patients with Sjogrens syndrome. These eight patients have certain clinical features in common with five patients described previously who had Sjogrens syndrome and reticulum cell sarcoma or pseudolymphoma. These findings provide further evidence that Sjogrens syndrome predisposes to the development of extrasalivary lymphoid abnormalities.

Androgenic Hormones Modulate Autoantibody Responses and Improve Survival in Murine Lupus

Antibodies to native DNA and to polyadenylic acid (Poly A) occur spontaneously and undergo a regulated switch from IgM to IgG during the course of autoimmune disease in NZB/NZW F(1) (B/W) mice. B/W females have higher titers and earlier commitment to 7S antibodies to DNA and Poly A, whereas B/W males bind DNA and Poly A primarily by 19S antibodies. We have performed castration experiments to determine the effects of sex hormones on this switch from IgM to IgG.NZB/NZW F(1) (B/W) mice were either castrated or subjected to sham surgery at 2 wk of age and studied for immunoglobulin class of antibodies to nucleic acids at 4, 6, and 7 mo post-surgery. Prepubertal castration of males caused premature death in 60% of mice. Castrated males had a significant decline in their serum testosterone concentration, an increase in DNA and Poly A binding, and an accelerated switch from 19S to 7S antibodies to nucleic acids. Castrated females had no change in mortality. However, castrated females given maintained androgen treatment had a decreased mortality compared to castrated females receiving estrogen (14 vs. 94%). The anticipated switch to 7S antibodies to Poly A was almost eliminated in castrated females. These results suggest that sex hormones modulate immunologic regulation and that androgenic hormones are protective in murine lupus.

The Pathogenesis of Autoimmunity in New Zealand Black Mice

This paper will review the immune disease of New Zealand Black (NZB) mice and their F1 hybrids produced by mating with New Zealand White mice (NZB/NZW). It will attempt to highlight important recent observations made in many laboratories around the world without exhaustively reviewing all papers written on the subject. Previous reviews have emphasized pathological changes and disease descriptions in New Zealand mice (Howie and Helyer, 1968; Helyer and Howie, 1963 a). The present effort will stress the immunological abnormalities of these mice. An attempt will be made to relate these immunological abnormalities with genetic and viral factors known to be important in their disease processes. The authors and their co-workers have studied approximately 20 000 NZB and NZB/NZW mice with regard to natural history, immunology, pathogenesis of disease and therapy. They will draw upon this experience when possible to fill in details not available in published reports.

Cyclophosphamide in Lupus Nephritis: A Controlled Trial

Abstract Thirteen women with lupus nephritis were hospitalized for a 10-week double-blind therapeutic trial comparing oral cyclophosphamide with placebo. Concurrent corticosteroid therapy, up to 30...

A conserved idiotype and antibodies to retroviral proteins in systemic lupus erythematosus.

22 of 61 systemic lupus erythematosus (SLE) patients produced antibodies to the p24 gag protein of HIV-1 demonstrated by Western blotting. 20 of these 22 patients (91%) also express the 4B4 idiotype (Id 4B4) previously identified on a human anti-Sm monoclonal antibody called 4B4. This represents an enrichment for this Id (seen in only 52% of SLE patients generally). Eight of these 22 SLE patients also have anti-Sm antibody activity. Sm partially inhibits the antibody binding of p24 gag suggesting immunologic cross-reactivity between the retroviral antigen p24 gag and the autoantigen Sm. Anti-Id 4B4 also inhibits p24 gag antibody binding by as much as 40%. Finally the monoclonal antibody 4B4 showed cross-reactivity to Sm and p24 gag. The following points emerge from our studies: (a) SLE patients make antibodies to p24 gag of HIV-1, (b) there is a relationship between immunity to p24 gag and a conserved idiotype, and (c) anti-Sm antibodies can cross-react with p24 gag.