Increased Chromogranin A Levels Indicate Sympathetic Hyperactivity in Patients with Rheumatoid Arthritis and Systemic Lupus Erythematosus

SILVIA CAPELLINO, TORSTEN LOWIN, PETER ANGELE, WERNER FALK, JOACHIM GRIFKA, and RAINER H. STRAUB

ABSTRACT.

Objective. Sympathetic hyperactivity is an unfavorable disease consequence in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) due to an increased risk of cardiovascular events. We aimed to identify a serum marker of the sympathetic nervous system, the adrenal chromogranin A (CHGA), in order to study sympathetic hyperactivity in RA and SLE.

Methods. Serum levels of CHGA were measured by radioimmunoassay in healthy subjects and patients with RA and SLE. CHGA immunofluorescence was performed in synovium of patients with RA and controls with osteoarthritis (OA). CHGA levels were measured in plasma, synovial fluid, and synovium superfusate in RA and OA controls.

Results. In healthy subjects, systemic CHGA levels correlated positively with age and plasma norepinephrine, indicating the sympathetic origin (p < 0.01). Serum CHGA levels were higher in RA and SLE than in healthy subjects (p < 0.001), which was particularly evident in female patients. Immunofluorescence revealed double-staining of CHGA and elastase-positive neutrophils in the synovium (but not with macrophages, T cells, fibroblasts, B cells, or tyrosine hydroxylase–positive cells). Density of CHGA+ cells was higher in RA synovium compared to OA controls. In OA controls and RA, CHGA levels were similar in plasma and synovial fluid, but levels in synovial tissue superfusate were markedly lower, which indicates that most of the CHGA is of systemic adrenal origin.

Conclusion. Increased level of CHGA is a good marker of systemic sympathetic hyperactivity. (First Release Dec 1 2007; J Rheumatol 2008;35:91-9)

Key Indexing Terms:

RHEUMATOID ARTHRITIS
OSTEOARTHRITIS
CHROMOGRANIN A
SYSTEMIC LUPUS ERYTHEMATOSUS
SYMPATHETIC NERVOUS SYSTEM

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From the Department of Internal Medicine I, the Department of Trauma Surgery, and the Department of Orthopedic Surgery, University Hospital Regensburg, Regensburg, Germany.

Supported by the Deutsche Forschungsgemeinschaft (DFG Research Unit FOR696).

S. Capellino, PhD; T. Lowin, PhD; W. Falk, PhD, Professor of Medicine; R.H. Straub, MD, Professor of Experimental Medicine, Rheumatologist, Department of Internal Medicine I; P. Angele, MD, Consultant of Trauma Surgery, Department of Trauma Surgery; J. Grifka, MD, Professor of Medicine, Chair, Department of Orthopedic Surgery, University Hospital Regensburg.

Address reprint requests to Dr. R.H. Straub, Department of Internal Medicine I, University Medical Center, D-93042 Regensburg, Germany. E-mail: rainer.straub@klinik.uni-regensburg.de

Accepted for publication September 4, 2007.

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