Can Lymphocytosis Be Associated With Sjogren's Syndrome? -- Comment From Reader and Author's Response

Robert I. Fox, MD, PhD; Robert Fox, MD

Disclosures

September 29, 2005

Question

Thank you for your response to a previous question published on Medscape titled "Can Lymphocytosis Be Associated With Sjögren's Syndrome?" In your response you mentioned that CD8+ cell counts may be increased in several conditions, including an association with cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infection. Do you know whether an elevated CD8+ T-cell count (or any other lymphocyte subset, resulting in an elevated total lymphocyte count) can be due to lymphocytic choriomeningitis virus?

Larry Bethoney, MD

Response from Robert I. Fox, MD, PhD and Robert Fox, MD

Background

The lymphocytosis may be relative (ie, an increased percentage of lymphocytes but not increased actual number of lymphocytes per mm3) or the lymphocytosis may be absolute (ie, an increase in the total number of lymphocytes per mm3 of blood). The most common finding is an increased relative percentage of lymphocytes due to the decrease in the number of neutrophils. Because the total white blood cell count is low due to the lower number of neutrophils and the number of lymphocytes remains normal, the clinical impression is relative lymphocytosis.

However, there are few patients in whom an absolute lymphocytosis may occur. An increase in actual number of lymphocytes per mm3 in a patient with suspected Sjögren's syndrome (SS) may suggest the presence of either an unexpected infection (such as HIV-1 or HTLV-1)[1] or a chronic lymphocytic leukemia.[] 2] Flow cytometry in the patient with absolute lymphocytosis may clarify these possibilities, as most SS patients show a polyclonal pattern of lymphocytes with a predominance of CD4+ T cells,[3] while diffuse infiltrative lymphocytosis syndrome exhibits predominantly CD8+ T cells.[1] Chronic leukemia states are most frequently B-cell chronic lymphocytic leukemia with CD5+/CD20+ B cells; less frequently, "T-gamma lymphomas" (characterized by a gamma T-cell receptor and markers associated with NK cells)[4] may be detected. Intercurrent infections such as EBV or CMV may mimic SS with lymphadenopathy and a positive antinuclear antibody test,[5] but these are uncommon and generally show a predominance of CD8+ lymphocytes on flow cytometry.[5] Rare cases of parvovirus B19 may lead to neutropenia and apparent lymphocytosis.[6]

Comment:

The mechanisms of neutropenia in systemic lupus erythematosus (SLE) and in SS are multifactorial.[7]Some patients may have decreased circulating neutrophils as a result of antineutrophil antibodies[8,9]that may be directed at Fc-gamma receptors resulting in increased rate of apoptosis[10]or clearance in the reticuloendothelial system of neutrophils.[11]Another factor leading to neutropenia may be anti-SSB/La autoantibodies; purified anti-SS B antibody can bind to normal human polymorphonuclear leukocytes (PMN)[12] and suppress their phagocytosis, while accelerating their apoptosis.[12]These in vitro results suggest that anti-SSB/La may play a role in autoimmune neutropenia and functional impairment of PMN in SS patients. Some SS and SLE patients may have autoantibodies against colony-stimulating factor or their receptors.[13]These patients are relatively refractory to treatment with recombinant granulocyte colony-stimulating factor (rGCSF).[14]Rare SS patients have neutropenia together with thrombocytopenia (Evans syndrome) in SS.[15]Other patients may have aplastic anemia[16]or myelodysplastic or myelofibrosis syndrome in the setting of their SS.[17,18]

However, it has also been suggested that the number of neutrophils in the body is maintained but that they are simply not reflected in the blood drawn at venipuncture.[19]For example, the chronic inflammatory process affects the blood vessels (especially within the reticulo-endothelial structures such as liver and spleen) to upregulate adhesive proteins. The activation of complement by immune complexes and antiendothelial antibodies[20]will cause the circulating neutrophils to marginate to the sides of the blood vessel.[19] Thus they appear to be decreased when peripheral blood is sampled (from the center of the vessel during venipuncture), while their actual number is maintained if a radiolabeled method is used to quantitate the neutrophils.

Comments

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