Characterization of T-Cell Large Granular Lymphocyte Leukemia Associated with Sjogren’s Syndrome—An Important but Underrecognized Association

https://doi.org/10.1016/j.semarthrit.2005.07.001Get rights and content

Objective

Patients with T-cell (CD3+) large granular lymphocyte (LGL) leukemia have a high prevalence of autoantibodies and associated autoimmune diseases. Sjogren’s syndrome may not be diagnosed unless specifically looked for. We set to determine the prevalence of Sjogren’s syndrome in LGL leukemia and its cytokine profile.

Methods

Every patient with a confirmed diagnosis of LGL leukemia diagnosed at a single academic medical center over the last 15 years was evaluated for Sjogren’s syndrome by questioning about sicca symptoms. In symptomatic patients, Schirmer’s test, rose bengal corneal staining, salivary flow rate measurement, autoantibody screening, and minor salivary gland biopsy were performed. Supernatants obtained from T-LGL leukemic cells following phytohemagglutinin (PHA) activation were analyzed for cytokine production by enzyme-linked immunosorbent assay and patients with or without Sjogren’s syndrome were compared with controls.

Results

Of 48 patients, 21 reported sicca symptoms and were enrolled in the study. In 8 patients Sjogren’s syndrome was ruled out. Thirteen patients had clear evidence of Sjogren’s syndrome according to accepted criteria (27%). None had rheumatoid arthritis, but 1 had limited scleroderma. Thus, 12/48 patients had primary Sjogren’s syndrome. Other autoimmune diseases were frequently present, in particular, immune cytopenias (n = 7) or thyroid autoimmunity (n = 6). Supernatants of T-LGL leukemia cells incubated with PHA revealed markedly increased levels of multiple cytokines (especially soluble interleukin 2 receptor, tumor necrosis factor alpha, IL-6, IL-8) compared with healthy controls. However, this increase was common to LGL leukemia patients with or without Sjogren’s syndrome.

Conclusions

Sjogren’s syndrome was commonly identified in the patients with T-cell LGL leukemia in this study. Upregulated cytokine production by the neoplastic cells may underlie some of the immune-mediated disorders common in these patients.

Section snippets

Patients

Kaplan Medical Center is an academic hospital located in central Israel, which serves as a referral center for a population of about 250,000. Over the years 1987 to 2002, 48 cases of T-LGL leukemia had been diagnosed and treated at our center by 1 of the authors (A.B.). All patients met the accepted criteria of T-LGL leukemia (1, 2, 11). Only 1 patient was treated for LGL leukemia before being evaluated for SS. She received prednisone and then cyclosporine A, and at the time of diagnosis of SS,

Patient’s Clinical Characteristics

Twenty-two patients with T-LGL leukemia reported sicca symptoms (3 unsolicited; all others, only when questioned) and 21 were studied. One patient who had both positive sicca symptoms and tests declined to participate. All but 2 were women. In 8 patients (6 women, 2 men) SS was ruled out by the combination of normal eye and salivary flow tests and a normal labial biopsy. The clinical characteristics of patients who had SS were not significantly different from those of patients in whom SS was

Discussion

This is the first reported series that actively examines T-cell LGL leukemia patients for the presence of SS. The association was previously recognized but did not extend further than a few case reports (5, 6). Only 2 patients were reported in any detail (6) and the others were either mentioned very briefly (11) or had SS secondary to RA (5). The finding that over a quarter of 48 patients with T-LGL leukemia studied had SS (Table 1) was unexpected and striking. This remarkable prevalence is

Acknowledgments

We acknowledge with thanks the expert pathological analysis done by Drs N. Sokolovski and M. Huszar (KMC, Rehovot), as well as the help of Dr V. Barak (Hadassah University Hospital, Jerusalem), Dr I. Lichman, and L. Bassous (KMC) in the laboratory studies.

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    Department of Medicine.

    Hematology Institute.

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