Mixed Cryoglobulinemia Shows Deficit of Treg Cells

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Blood First Edition Paper, prepublished online December 18, 2003

Submitted September 3, 2003

Accepted November 13, 2003

CD4+CD25+ regulatory T cells deficiency in patients with hepatitis C-

mixed cryoglobulinemia vasculitis

Olivier Boyer, Saadoun, n Abriol, Dodille, Jean-

Piette, Patrice Cacoub, and Klatzmann*

UMR 7087, CNRS/UPMC, Paris, France

Service de Medecine Interne, Hopital Pitie-Salpetriere, Paris, France

Chronically-infected hepatitis C virus (HCV) patients often develop

mixed cryoglobulinemia (MC), a B cell proliferative disorder with

polyclonal activation and autoantibody production. We investigated if

MC is associated with a deficit of CD4+CD25+ immuno-regulatory T-

cells (Treg), which have been shown to control autoimmunity.

Since Treg express higher amounts of CD25 than activated CD4+ T-

cells, we analyzed blood CD4+CD25high Treg in 69 untreated

chronically-infected HCV patients. Treg frequency in patients without

MC (8.8±2.3%) or with asymptomatic MC (7.4±2.1%) was comparable to

that of healthy controls (7.9±1.3%). In contrast, it was

significantly reduced in symptomatic MC patients (2.6±1.2%, p<0.001),

even when compared to a panel of untreated HCV-negative patients with

different inflammatory disorders (6.2±0.8%, p<0.0001). In symptomatic

MC patients, the purified remaining CD4+CD25+ T-cells retained

suppressive activity in vitro.

These results, together with experimental data showing that depletion

of Treg induces autoimmunity, suggest a major role of Treg deficiency

in HCV-MC vasculitis and are the first report of a quantitative Treg

deficiency in virus-associated autoimmunity.