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BMC Musculoskeletal Disorders

, 16:129

Pathophysiology of musculoskeletal disorders


BackgroundImmunoglobulin Ig G4-related disease IgG4-RD is characterized by elevated serum IgG4 and infiltration of IgG4 plasma cells into multiple organs. It is not known whether serum IgG4 is autoreactive in IgG4-RD.

MethodsWe measured anti-nuclear antibody ANA in 19 IgG4-RD cases, determined IgG subclasses of the ANA, and compared them with those of other systemic autoimmune diseases systemic lupus erythematosus, Sjögren’s syndrome, systemic sclerosis, and polymyositis, using subclass-based ANA test indirect immunofluorescence.

Results58 % of IgG4-RD cases were ANA-positive cut-off: 1:40. Whereas their subclass of ANA was predominantly IgG2, we observed no IgG4-type ANA. In systemic autoimmune diseases, subclasses of ANA were mostly IgG1, 2, or 3, but IgG4-type ANA was very rarely detected. We also found several patients in whose serum ANA patterns differed among IgG subclasses, probably due to the difference of corresponding autoantigens.

ConclusionsAlthough IgG4 is highly elevated in sera of IgG4-RD patients, their ANA do not include IgG4 subclass. These results offer new insight into the role of IgG4 and the pathogenesis of IgG4-RD, implying that each IgG subclass tends to cover its own spectrum of antigens, and IgG4 is not preferentially used to make ANA.

KeywordsIgG4-related disease Systemic autoimmune disease IgG subclass Autoantibody Anti-nuclear antibody AbbreviationsANAAnti-nuclear antibody

ANCAAnti-neutrophil cytoplasmic antibody

AIPAutoimmune pancreatitis

CCPCyclic citrullinated peptides

dsDNADouble-stranded deoxyribonucleic acid


ELISAEnzyme-linked immunosorbent assay

GPAGranulomatosis with polyangiitis

HLAHuman leukocyte antigen

IgG4-RDImmunoglobulin G4-related disease

IIFIndirect immunofluorescence


PLA2RPhospholipase A2 receptor



PTSIPancreatic secretory trypsin inhibitor

RARheumatoid arthritis


SLESystemic lupus erythematosus

SSSjögren’s syndrome

SScSystemic sclerosis.

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Autor: Kazuhiro Kiyama - Hajime Yoshifuji - Tsugumitsu Kandou - Yuji Hosono - Koji Kitagori - Ran Nakashima - Yoshitaka Imura - Na


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