Selective autoantibody production against CCL3 is associated with human type 1 diabetes mellitus and serves as a novel biomarker for its diagnosis.
We have recently demonstrated that patients suffering from chronic autoimmune diseases develop an autoantibody response against key mediators that participate in the initiation and progression of these diseases. In this paper, we show that patients with type 1 diabetes mellitus (T1DM), but not those suffering from several other inflammatory autoimmune diseases, display a selective autoantibody titer to a single CC chemokine named CCL3. From the diagnostic point we show that this response could be used as a biomarker for diagnosis of T1DM, a disease that is currently diagnosed by autoantibodies to competitive anti-insulin Abs, islet cell Abs, and glutamic acid decarboxylase Abs. We show that our currently suggested biomarker is more reliable than each of the above alone, including diagnosis of T1DM at its preclinical stage, and could therefore be used as a novel way for diagnosis of T1DM. These Abs were found to be neutralizing Abs. It is possible, though hard to prove, that these Abs participate in the natural regulation of the human disease. Hence, it has previously been shown by others that selective neutralization of CCL3 suppresses T1DM in NOD mice. Theses results together with ours suggest CCL3 as a preferential target for therapy of T1DM.
Shehadeh
Naim
N
Department of Immunology, Rambam Medical Center, Technion, Haifa, Israel.
Pollack
Shirly
S
Wildbaum
Gizi
G
Zohar
Yaniv
Y
Shafat
Itay
I
Makhoul
Reem
R
Daod
Essam
E
Hakim
Fahed
F
Perlman
Rina
R
Karin
Nathan
N
D000293:Adolescent; D000328:Adult; D000917:Antibody Formation / Q000276:immunology*; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D002460:Cell Line; D054405:Chemokine CCL3 / Q000097:blood* / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis* / Q000276:immunology*; D006801:Humans; D007223:Infant
D001323:Autoantibodies; D015415:Biomarkers; D054405:Chemokine CCL3