Biomaterial Database

Autoantibody production in Sjögren's syndrome: a hypothesis regarding defects in somatic diversification of germ line encoded genes. 1988

R I Fox, and S Fong, and P P Chen, and T J Kipps

Department of Basic and Clinical Research, Research Institute of Scripps Clinic, La Jolla, California 92037.

Patients with primary Sjögren's syndrome (SS) have rheumatoid factor (anti-IgG Fc antibody, RF) in their sera that contains a crossreactive idiotype (CRI) defined by monoclonal antibody 17-109. This CRI is shared by SS patients and certain patients with Waldenstrom's macroglobulinemia. This CRI was not found in increased frequency in RF from rheumatoid arthritis patients lacking SS. The structural basis for this CRI is the highly conserved kappa chain of the Vk IIIb sub-subgroup. In SS patients, the CRI is present on both IgA RF and IgM RF, accounting for 5-20% of the total RF. Recent studies have shown that a germ line encoded kappa variable region gene (Humkv 325, cloned from a placental DNA library) has DNA sequence that encodes the variable region amino acid sequences of CRI positive kappa chains. Using MoAb 17-109, we have been able to determine the tissue distribution of CRI+ B-cells. We found an increased frequency in the salivary gland biopsies of SS patients and also in their intestinal mucosal tissues (i.e. Peyer's patch). In comparison, we also detected an increased frequency of CRI+ B-cells in the Peyer's patch regions of normals. Taken together, these results suggest that CRI+ B-cells may play an important role in normal mucosal immunity and these CRI+ B-cells have migrated to the salivary gland in SS patients as part of the inflammatory process directed at autoantigens or exogenous antigen(s) located at a mucosal surface.(ABSTRACT TRUNCATED AT 400 WORDS)

UI	MeSH Term	Description	Entries
D007130	Immunoglobulin Idiotypes	Unique genetically-controlled determinants present on ANTIBODIES whose specificity is limited to a single group of proteins (e.g., another antibody molecule or an individual myeloma protein). The idiotype appears to represent the antigenicity of the antigen-binding site of the antibody and to be genetically codetermined with it. The idiotypic determinants have been precisely located to the IMMUNOGLOBULIN VARIABLE REGION of both immunoglobin polypeptide chains.	Idiotypes, Immunoglobulin,Ig Idiotypes,Idiotype, Ig,Idiotype, Immunoglobulin,Idiotypes, Ig,Ig Idiotype,Immunoglobulin Idiotype
D008258	Waldenstrom Macroglobulinemia	A lymphoproliferative disorder characterized by pleomorphic B-LYMPHOCYTES including PLASMA CELLS, with increased levels of monoclonal serum IMMUNOGLOBULIN M. There is lymphoplasmacytic cells infiltration into bone marrow and often other tissues, also known as lymphoplasmacytic lymphoma. Clinical features include ANEMIA; HEMORRHAGES; and hyperviscosity.	Lymphoma, Lymphoplasmacytoid,Macroglobulinemia,Familial Waldenstrom's Macroglobulinaemia,Lymphoma, Lymphocytic, Plasmacytoid,Primary Macroglobulinemia,Waldenstrom's Macroglobulinaemia,Waldenstrom's Macroglobulinemia,Familial Waldenstrom Macroglobulinaemia,Familial Waldenstroms Macroglobulinaemia,Lymphomas, Lymphoplasmacytoid,Lymphoplasmacytoid Lymphoma,Lymphoplasmacytoid Lymphomas,Macroglobulinaemia, Familial Waldenstrom's,Macroglobulinaemia, Waldenstrom's,Macroglobulinemia, Primary,Macroglobulinemia, Waldenstrom,Macroglobulinemia, Waldenstrom's,Waldenstrom Macroglobulinaemia,Waldenstrom's Macroglobulinaemia, Familial,Waldenstroms Macroglobulinaemia,Waldenstroms Macroglobulinemia
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D005803	Genes, Immunoglobulin	Genes encoding the different subunits of the IMMUNOGLOBULINS, for example the IMMUNOGLOBULIN LIGHT CHAIN GENES and the IMMUNOGLOBULIN HEAVY CHAIN GENES. The heavy and light immunoglobulin genes are present as gene segments in the germline cells. The completed genes are created when the segments are shuffled and assembled (B-LYMPHOCYTE GENE REARRANGEMENT) during B-LYMPHOCYTE maturation. The gene segments of the human light and heavy chain germline genes are symbolized V (variable), J (joining) and C (constant). The heavy chain germline genes have an additional segment D (diversity).	Genes, Ig,Immunoglobulin Genes,Gene, Ig,Gene, Immunoglobulin,Ig Gene,Ig Genes,Immunoglobulin Gene
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D001323	Autoantibodies	Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.	Autoantibody
D001402	B-Lymphocytes	Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.	B-Cells, Lymphocyte,B-Lymphocyte,Bursa-Dependent Lymphocytes,B Cells, Lymphocyte,B Lymphocyte,B Lymphocytes,B-Cell, Lymphocyte,Bursa Dependent Lymphocytes,Bursa-Dependent Lymphocyte,Lymphocyte B-Cell,Lymphocyte B-Cells,Lymphocyte, Bursa-Dependent,Lymphocytes, Bursa-Dependent