Systemic Sclerosis

An Update

Uwe-Frithjof Haustein, MD, PhD

Disclosures

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.

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....