Systemic Sclerosis

An Update

Uwe-Frithjof Haustein, MD, PhD


Lab Med. 2011;42(9):562-572. 

In This Article

Immune System

T lymphocytes

The location of inflammatory infiltrates, mainly CD4-T cells, around blood vessels and at sites of active connective tissue formation suggests a pathogenetic role for them.[49,52] Obviously, regulatory (suppressor) T cells are functionally impaired. Levels of lymphocyte- and monocyte-derived cytokines, such as IL-1, IL-2, IL-4, IL-6, and receptors (rec), such as soluble CD4 and IL-2R, are elevated in the circulation[54] (Table 2). Interleukin-2 can induce up to 40-fold elevations in the secretion of active TGFβ by monocytes. Activated T cells may produce IL-2, which upregulates TGFβ in monocytes that in turn activates FBs to secrete and organize the elements of the ECM. Lymphocyte and monocyte ligands, L-selectin, sialated glycoproteins, lymphocyte function-associated antigen 1 (LFA-1) (CD11a, CD18), and Mac1 (CD11b, CD18) bind to the EC rec and modulate the migration of these cells. In addition, lymphocytes respond to chemotactic stimuli, activate FBs via ICAM-1, and bind to non-cellular integrins expressed on collagen and fibronectin via surface VLA-1 (CD49a, CD29) and VLA-4 (CD49d, CD29). These processes explain the reciprocal activation of immune cells and FBs by direct cell contact as well as by the indirect effects of soluble cytokines.[52,53]

B Lymphocytes

B cells are the sources of the Auto-ab representing hall-marks of SSc. Beside this, B cells secrete B cell activating factor (BAFF). Increased serum levels of BAFF positively correlate with the severity of skin fibrosis. CD19, a critical cell-surface signal transduction molecule, is relatively specifically over-expressed in naïve and memory B cells in SSc, indicating an abnormal regulation of the response regulator function and expression that may lead to loss of tolerance and to autoimmunity.[54] In addition, this may be interpreted as linkage between autoimmunity and fibrosis.


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