Epub Nov Molecular and immunohistochemical studies demonstrated an association with Campylobacter jejuni. IPSID is a variant of the B-cell lymphoma of mucosa-associated lymphoid tissue MALT , which involves mainly the proximal small intestine resulting in malabsorption, diarrhea, and abdominal pain. IPSID lymphomas reveal excessive plasma cell differentiation and produce truncated alpha heavy chain proteins lacking the light chains as well as the first constant domain. The corresponding mRNA lacks the variable heavy chain V H and the constant heavy chain 1 C H 1 sequences and contains deletions as well as insertions of unknown origin. The encoding gene sequence reveals a deletion of V region and parts of C H 1 domain.
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Thus, the length of the basic polypeptide subunit varies from patient to patient and in most instances it is between half and three fourths the size of its normal counterpart.
The carboxy terminal structure and conformational integrity remain intact. The dotted areas represent deleted variable and first constant regions of amino terminus of the heavy chain blue as well as missing entire light chain orange.
The normal structure of the immunoglobulin molecule resumes at the beginning of the hinge region green. The carboxy terminal COO- portion of the polypeptide is intact. It also contains an in-frame insert of unknown origin between the leader peptide and the normal CH2 and CH3 coding sequences. Their structure suggests that they result from alternative splicing process. These sequences do not resemble any normal human genomic DNA. The absence of homology between these insertions could not support the hypothesis of infectious nonhuman DNA, either.
They may represent highly altered sequences from human Ig locus. In all cases, most, or all, of the V region is deleted as is the sequence starting in the switch region and extending through part, or all, of the CH1 domain. Studies reported from various laboratories suggested that independent structural gene abnormalities are at least partially responsible for the uniform absence of detectable light chain production in HCD.
In contrast to most normal and neoplastic Ig-producing cells, there is excess of heavy to light chain mRNA as well as protein. Transcription can be increased by fusing the HCD cell line to murine myeloma cell line or transfecting the defective light chain gene into a murine plasma cell. Other findings suggested that the examined HCD cells either lack a transcription factor present in mature plasma cells or have a functional repressor of light chain transcription.
Plasma cells in mucosal tissue assemble polymeric IgA intracellularly from monomeric IgA. Normal plasma IgA is monomeric, while mucosal IgA is dimeric or tetrameric. It contains joining J chains that help recognize the receptor pIgR expressed on basolateral surfaces of adjacent epithelial cells.
This could be expected because in IPSID the crypts are atrophic and highly dispersed in contrast to celiac disease where they are hyperplastic Figure 1C-D. In one patient, rearrangement resulted from translocation 9;14 in 21 of 23 mitoses. Pathogenesis The search for pathogenic factors was related to the well-known unique features of IPSID its ethnic and geographic distribution as well its response to antibiotics at least in the early stages.
A follow-up retrospective analysis of archival intestinal biopsy specimen disclosed Campylobacter species in 4 of 6 additional patients with IPSID, using fluorescent in situ hybridization FISH and immunohistochemical techniques. C jejuni is an initiating factor in chronic autoimmune disease such as Guillan-Barre syndrome and reactive arthritis.
Heavy chain disease
Immunoproliferative small intestinal disease (IPSID): a model for mature B-cell neoplasms.