Thomas M. Chused

Increased Risk of Lymphoma in Sicca Syndrome

The risk of cancer was ascertained in 136 women with sicca syndrome followed at the National Institutes of Health (NIH). Seven patients developed non-Hodgkins lymphoma from 6 months to 13 years after their first admission to NIH. This was 43.8 times (P less than 0.01) the incidence expected from the rates of cancer prevailing among women of the same age range in the general population during this time. In addition, three cases of Waldenströms macroglobulinemia occurred in this study group. Eight patients developed cancers other than lymphoma, similar to the number expected based on the rates prevailing in the general population. Patients with a history of parotid enlargement, splenomegaly, and lymphadenopahy had an increased risk of lymphoma. These clinical conditions did not appear to be early manifestations of undiagnosed lymphoma but rather seemed to identify a subgroup of patients with sicca syndrome with marked lymphoid reactivity, who had a particularly high risk of subsequently developing lymphoma.

Sjögren's Syndrome (Sicca Syndrome): Current Issues

This paper outlines the clinical, serologic, and immunogenetic differences and similarities of Sjögrens syndrome alone (primary) and Sjögrens syndrome associated with rheumatoid arthritis and systemic lupus erythematosus (secondary). The immunoregulation in Sjögrens syndrome is discussed and the incidence of immune complex-like material, its nature, pathophysiology, and clearance by the Fc recptor of the reticuloendothelial system presented.

Human neutrophils increase expression of C3bi as well as C3b receptors upon activation.

We used monoclonal antibodies and flow cytometry to study the expression of the receptors for the complement fragments C3bi (CR3) and C3b (CR1) on human polymorphonuclear neutrophil leukocytes (PMN). Expression of both receptors was minimal on cells stained in anticoagulated whole blood incubated at 0 degree or 37 degrees C. PMN isolated with Percoll density gradients and held at 0 degree C also had only minimal expression of both receptors. With the isolated cells, however, a spontaneous increase in expression of both receptors occurred upon warming to 37 degrees C. This did not represent complete expression of either receptor since additional increments in surface expression could be induced upon stimulation with N-formyl-methionyl-leucyl-phenylalanine or Raji cell supernatant. The increases in complement receptor (CR) expression appeared to be specific since there were no changes in expression of the Fc gamma receptor or beta-2-microglobulin under any of these conditions. The increased CR expression seems to involve translocation from an intracellular pool since it is complete within minutes and is not blocked by puromycin or cycloheximide. These results demonstrate that both CR3 and CR1 expression increase rapidly upon activation of PMN and that isolated cells can be used to study this phenomenon, which may be a critical part of neutrophil function in vivo.

Sjögren-Type Syndrome After Allogeneic Bone-Marrow Transplantation

Four patients, treated for hematologic disorders with bone-marrow transplants from HLA-identical siblings, spontaneously complained of dry eyes 8 to 12 months after transplantation. Four allograft recipients and two recipients of autologous bone-marrow transplants were evaluated for xerophthalmia and xerostomia. Three allogeneic marrow recipients had evidence of keratoconjunctivitis sicca, and two had decreased parotid gland function. All four allograft recipients had minor salivary gland histopathology identical to that of Sjögrens syndrome. The severity of symptoms and histologic lesions corresponded with the severity of chronic graft-versus-host disease. In addition, one patient developed sclerodermatous skin changes, another had discoid lupus erythematosus, and two patients had laboratory evidence of cholestasis. None of the patients had autoantibodies but all had hypergammaglobulinemia. In contrast, none of the recipients of autologous bone marrow had clinical, laboratory, or histologic findings resembling Sjögrens syndrome.

Differences in the clinical manifestations of sicca syndrome in the presence and absence of rheumatoid arthritis

In this restrospective study we review the clinical features of patients with the sicca syndrome in the presence and absence of rheumatoid arthritis. All patients were followed at the National Institutes of Health for at least five years after the diagnosis of sicca syndrome was established. Twenty-two patients had sicca syndrome alone, and 21 patients had definite rheumatoid arthritis and the sicca syndrome. Rheumatoid arthritis tended to precede the developement of sicca syndrome. The mean age at diagnosis of sicca syndrome is the same in both groups. No significant differences in serum innumoglobulins, the third component of complement (C3), rheumatoid factor titer and salivary histopathology were found. However, the clinical features were quite distinct. Patients with sicca syndrome alone had a significantly greater frequency of recurrent parotitis, Raynauds phenomenon, purpura, lymphadenopathy, myositis and renal involvement. The clinical characteristics of these two groups coupled with the known serologic and genetic differences suggest that sicca syndrome alone is a distinct pathologic entity.

Sjögren's Syndrome Associated with HLA-Dw3

Abstract Sjogrens syndrome is associated with a serologically defined histocompatibility antigen of the HLA-B locus, HLA-B8. Another closely linked locus, HLA-D, determines lymphocyte-defined cell...

Correlation between Immunologic Function and Clinical Subpopulations of Patients with the Acquired Immune Deficiency Syndrome

The present study was designed to determine whether there was a significant correlation between the clinical presentation of patients with AIDS or AIDS-related illnesses and the degree of their underlying immunologic abnormalities. In 17 patients who presented with opportunistic infections, the mean number of T4 lymphocytes was 34/mm3 and the mean proliferative response to phytohemagglutinin 26,000 cpm; in 12 patients who presented with Kaposis sarcoma alone, the mean number of T4 cells was 231/mm3 and the mean proliferative response to phytohemagglutinin, 32,809 cpm; and in nine patients with the lymphadenopathy syndrome, the mean number of T4 cells was 703/mm3 and the mean proliferative response to phytohemagglutinin, 49,317 cpm. These findings suggest that those patients who present with opportunistic infections as their initial clinical manifestation of AIDS may represent a subgroup with a more severe immunologic derangement prior to clinical diagnosis. Thus, in those who have a predisposition to Kaposis sarcoma, this disease will often develop, prior to the development of T cell dysfunction, to the degree of that in those who present with opportunistic infections. This finding is of importance in attempts to understand the pathogenesis of this syndrome and in the design of therapeutic trials.

Genetic differences between primary and secondary sicca syndrome.

SICCA syndrome occurs alone or in association with another autoimmune disease, frequently rheumatoid arthritis. We recently proposed that sicca syndrome be termed primary when it occurs alone and s...

Heterogeneity of immunoregulatory T-cell subsets in systemic lupus erythematosus: Correlation with clinical features

Immunoregulatory T-cell subsets as defined by differentiation antigens were studied in 32 patients with systemic lupus erythematosus (SLE) and 16 healthy persons using the monoclonal antibodies OKT 3 or anti-Leu 4 (T cells), anti-Leu 2a (suppressor/cytotoxic cells) and anti-Leu 3a (helper/inducer cells). Compared with the 95 percent confidence limits in control subjects, decreases or increases of Leu 3a+ cells were observed in 23 patients, whereas abnormal percentages of Leu 2a+ cells were observed in only 10 patients (p less than 0.002). The ratio of Leu 3a+ to Leu 2a+ cells varied over a much broader range (0.31 to 4.14) in patients with SLE than in control subjects (95 percent confidence limit 1.04 to 2.20). Furthermore, the helper:suppressor ratio correlated significantly (p less than 0.001) with a numerical clinical characterization of the patients. A low helper: suppressor ratio was observed in patients with severe renal disease, thrombocytopenia and onset of SLE by 20 years of age. Patients with a high helper:suppressor ratio had multisystem disease including lymphadenopathy, but only rarely SLE renal disease. Patients with a normal helper:suppressor ratio had the most widespread multisystem disease, often involving the kidneys and the central nervous system. The ratio was not correlated with duration of illness, disease activity or corticosteroid dosage in the patients examined. The study suggests that SLE is not one disease entity, but rather a symptom complex with different immunoregulatory abnormalities and associated manifestations.

Immune complex glomerulonephritis in sicca syndrome.

In three patients with the sicca syndrome (Sjögrens syndrome), who were followed for one to seven years, glomerulonephritis developed. None of these patients fulfilled the diagnostic criteria for systemic lupus erythematosus. All of these patients had circulating immune complexes as detected by the Clq binding assay. Glomerular histology by light and electron microscopy revealed changes compatible with membranoproliferative glomerulonephritis in two of the patients and membranous glomerulonephritis in the third. All patients showed rapid improvement in renal function following moderate doses of corticosteroids. In addition, the treatment decreased the level of circulating immune complexes in two patients who were followed for a sufficient period of time.