Elevated Numbers of Proliferating Mononuclear Cells in the Peripheral Blood of Psoriatic Patients Correlate with Disease Severity

Abstract

Although psoriasis is characterized by the accumulation of activated proliferating lymphoid cells in the psoriatic skin lesion, it is not known whether these cells are activated and proliferating before entry into the psoriatic plaque. The current study evaluates the number and phenotype of proliferating lymphoid cells in the blood of psoriatic patients. Proliferation of peripheral blood mononuclear cells was evaluated on cytospun preparations of these cells using autoradiographic techniques after pulsing the mononuclear cells with 3H-methyl thymidine for 2 h. The phenotypes of the labeled peripheral blood mononuclear cells were determined combining autoradiography and immunohistochemistry with monoclonal antibodies directed at CD3, CD4, CD8, CD11c, CD22, and human leukocyte antigen-DR. The data demonstrated elevated numbers of proliferating lymphoid cells in the blood of psoriatic patients compared with normal nonpsoriatic volunteers (p < 0.01). Furthermore, the number of circulating proliferating mononuclear cells increased significantly with increasing psoriasis skin disease severity (correlation coefficient 0.95; p < 0.0001). When the phenotype of the proliferating cells in the blood was examined, the numbers of T cells (CD3+, CD4+, CD8+ cells), B cells (CD22+ cells), monocytes (CD11c+ cells), and human leukocyte antigen-DR+ cells were significantly elevated compared with nonpsoriatic skin (p < 0.01) and increased with increasing disease activity (correlation coefficient range 0.48-0.74; p < 0.05). The data suggest a generalized systemic activation of T, B, and monocytic cells that results in labeling of up to 0.16% of the circulating mononuclear cells with 3H-methyl thymidine (i.e., proliferating and presumably activated) when assayed in vitro.

Epidermal HLA-DR and the enhancement of cutaneous reactivity to superantigenic toxins in psoriasis

“…Indeed, increased numbers of activated T cells have been described in psoriatics (41). Of note, PBMCs from psoriatic patients have been reported to respond more vigorously to SEB and TSST-1 in vitro than have normal control patient populations (43). As seen in the present study, this…”

Lymphoma Rates Are Low but Increased in Patients With Psoriasis

“…5 Other investigators have also demonstrated increased B-lymphocyte activity in patients with psoriasis, which suggests broad immune activation. [6][7][8] Since psoriasis is a disease of immune activation, it has been hypothesized that patients with psoriasis may be at increased risk for developing lymphoproliferative malignancies. 9 Furthermore, treatment with immunosuppressive medications used to treat psoriasis may be an independent risk factor for developing lymphoproliferative malignancies 10 ; or it may be that having psoriasis and being exposed to immunomodulating medications results in an increased risk of developing lymphomas.…”

CD69, HLA-DR and the IL-2R Identify Persistently Activated T Cells in Psoriasis Vulgaris Lesional Skin: Blood and Skin Comparisons by Flow Cytometry

“…Studies had shown either increases [54,55], or no changes [56,57] in activated T cell populations in psoriatic vs. control blood comparisons. Our results, from a severely affected patient population, show that psoriasis vulgaris appears to be different from the other autoimmune disorders and from controls since we found increases in CD25 and did not find increases of CD69 or HLA-DR on circulating T cells as found in other chronic autoimmune disorders [58][59][60].…”