Repetitive hinge region sequences in human IgG3: isolation of an 11,000-dalton fragment.

Adlersberg, Jay B.; Frangione, Blas

doi:10.1073/pnas.72.2.723

Cited by 26 publications

(6 citation statements)

References 24 publications

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“…IgG3 is the strongest complement activator [36], and furthermore, IgG3 is more flexible as a result of a longer hinge region [37]. In this study, we observed a significantly higher serum level of IgG1 against bacterial HSP60 compared with the level of IgG3.…”

Section: Discussionsupporting

confidence: 47%

Increased Levels of IgG Antibodies against Human HSP60 in Patients with Spondyloarthritis

et al. 2013

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Spondyloarthritis (SpA) comprises a heterogeneous group of inflammatory diseases, with strong association to human leukocyte antigen (HLA)-B27. A triggering bacterial infection has been considered as the cause of SpA, and bacterial heat shock protein (HSP) seems to be a strong T cell antigen. Since bacterial and human HSP60, also named HSPD1, are highly homologous, cross-reactivity has been suggested in disease initiation. In this study, levels of antibodies against bacterial and human HSP60 were analysed in SpA patients and healthy controls, and the association between such antibodies and disease severity in relation to HLA-B27 was evaluated.Serum samples from 82 patients and 50 controls were analysed by enzyme-linked immunosorbent assay (ELISA) for immunoglobulin (Ig)G1, IgG2, IgG3 and IgG4 antibodies against human HSP60 and HSP60 from Chlamydia trachomatis, Salmonella enteritidis and Campylobacter jejuni. Disease severity was assessed by the clinical scorings Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI).Levels of IgG1 and IgG3 antibodies against human HSP60, but not antibodies against bacterial HSP60, were elevated in the SpA group compared with the control group. Association between IgG3 antibodies against human HSP60 and BASMI was shown in HLA-B27+ patients. Only weak correlation between antibodies against bacterial and human HSP60 was seen, and there was no indication of cross-reaction.These results suggest that antibodies against human HSP60 is associated with SpA, however, the theory that antibodies against human HSP60 is a specific part of the aetiology, through cross-reaction to bacterial HSP60, cannot be supported by results from this study. We suggest that the association between elevated levels of antibodies against human HSP60 and disease may reflect a general activation of the immune system and an increased expression of human HSP60 in the synovium of patients with SpA.

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Section: Discussionsupporting

confidence: 47%

Increased Levels of IgG Antibodies against Human HSP60 in Patients with Spondyloarthritis

et al. 2013

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“…When isolated from the serum and analyzed, it showed an apparent NH2-terminal deletion of the entire V and CHI domain, with sequence starting within the hinge (4).…”

Section: Introductionmentioning

confidence: 99%

Gamma heavy chain disease in man. Genomic sequence reveals two noncontiguous deletions in a single gene.

Alexander¹,

Anicito²,

Buxbaum³

1988

J. Clin. Invest.

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A genomic clone was isolated from a human lymphoid cell line which synthesized an NHrterminally deleted gamma3 heavy chain disease protein. Nucleotide sequence analysis revealed a normal sequence from 310 bp 5' to the initiator ATG through the codon for VH amino acid 14. Amino acid 15 was derived from the codon for the last J4 amino acid. Thus, the clone contained a deletion of the codons for the VH region beyond amino acid 14, as well as those for the entire D region and most of the J coding region. Some sequence abnormalities were observed in the 400 bp after the deletion. Beyond this, there was excellent homology to published J and intervening sequences, including those containing the enhancer elements. The 1,200-bp switch region was abruptly interrupted by a sequence corresponding to the 3' one-third of CHi. Thus, a second deletion eliminated the acceptor splice site at the 5' end of CHi. When splicing of the primary RNA transcript occurred, the truncated VH region was joined via the J4 donor splice site to the next available acceptor site 5' to the first hinge exon. Hence, the aberrant serum protein was the product of two deletions and a splice correction as well as postsynthetic NH2-terminal proteolysis.

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“…A y3 HCD protein was isolated from the serum of patient OMM and shown to have a monomeric molecular weight of 40,000 and an unblocked NH2 terminus (3). It had undergone an extensive NH2-terminal deletion with a homogeneous sequence starting within the hinge.…”

mentioning

confidence: 99%

gamma Heavy chain disease in man: cDNA sequence supports partial gene deletion model.

Alexander¹,

Steinmetz²,

Barritault³

et al. 1982

Proc. Natl. Acad. Sci. U.S.A.

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Human y heavy chain disease (HCD) is characterized by the presence in serum of a short monoclonal Ig y chain unattached to light chains. Although most HCD proteins have internal deletions, in some the defect is NH2-terminal. The OMM v3 HCD serum protein is of the latter type, having undergone an extensive NH2-terminal deletion with a sequence starting within the hinge. A cell line synthesizing the OMM protein has enabled us to study the biogenesis ofthe abnormal molecule. In vitro translation ofisolated mRNA yields a protein containing a hydrophobic NH2-terminal leader sequence. In the intact cell, the precursor molecule is processed normally to yield a protein with an NH2-terminal sequence homologous to the beginning of the variable (V) region. The nucleotide sequence of cDNA prepared from the OMM mRNA encodes a 19-amino acid leader followed by the first 15 residues ofthe V region. An extensive internal deletion encompasses the remainder of the V and the entire CHI domain. Immediately following the short V region, there is information in the cDNA for the entire normal hinge. The primary synthetic product is thus an internally deleted molecule that undergoes postsynthetic degradation to yield the NH2-terminally deleted serum protein.The structure of the OMM mRNA suggests that the protein abnormality results from a partial gene deletion rather than defective splicing.In heavy chain disease (HCD), a naturally occurring human lymphoproliferative disorder, variant monoclonal Ig heavy (H) chain fragments are found in the patients' serum or urine. HCD proteins of the 'y class have been studied in detail, although those ofthe a and. y classes have also been described (1, 2). The abnormal serum proteins of the y class all show complete deletion of the CHi domain of the constant (C) region. Additional features separate the proteins into three types. Most ofthe variant molecules studied to date have a normal or aberrant NH2-terminal variable (V)-region sequence ofvariable size, followed by an extensive internal deletion encompassing most of the V region and the CHL domain. Normal structure usually resumes at the beginning ofthe hinge. In the second group, the deletion continues through the hinge, with normal sequence starting in the CH2 domain. Least frequently, y HCD proteins are found that lack the entire V and CHI domains. In such cases, the serum protein sequence starts within the hinge, and it is therefore unclear whether the molecules are of degradative or synthetic origin.A y3 HCD protein was isolated from the serum of patient OMM and shown to have a monomeric molecular weight of 40,000 and an unblocked NH2 terminus (3). It had undergone an extensive NH2-terminal deletion with a homogeneous sequence starting within the hinge. In addition to the HCD protein, the patient's serum also contained a homogeneous (y3)2A2 molecule with apparently normal H and light (L) chains (4). Because the HCD protein was NH2-terminally deleted, it was not possible to tell whether it was the product of partial proteolytic degrad...

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Repetitive hinge region sequences in human IgG3: isolation of an 11,000-dalton fragment.

Cited by 26 publications

References 24 publications

Increased Levels of IgG Antibodies against Human HSP60 in Patients with Spondyloarthritis

Increased Levels of IgG Antibodies against Human HSP60 in Patients with Spondyloarthritis

Gamma heavy chain disease in man. Genomic sequence reveals two noncontiguous deletions in a single gene.

gamma Heavy chain disease in man: cDNA sequence supports partial gene deletion model.

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