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The molecular pathology of Sjogren's syndrome. Applications to the prediction of early lymphoma

Jordan, Richard Charles Kennedy; (1995) The molecular pathology of Sjogren's syndrome. Applications to the prediction of early lymphoma. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Sjogren's syndrome (SS) is an autoimmune disease characterised by lymphocyte mediated destruction of exocrine glands producing the characteristic symptoms of dry eyes and dry mouth. The syndrome is also characterised by a generalised lymphoproliferation which predisposes patients to the development of malignant lymphoma. Although the relative risk of lymphoma development is estimated to be 44 times that of the general population, few reliable markers exist to predict outcome in individual cases. This study examined the prevalence of monoclonality of immunoglobulin (lg) components in salivary gland lesions from patients with SS. In the first two parts of the study, large series of labial salivary gland (LSG) biopsies from patients under investigation for SS were examined for lg heavy chain gene monoclonality using the polymerase chain reaction (PCR) and for light chain restriction of [kappa] and [lambda] mRNA using in situ hybridisation (ISH). The prevalence of monoclonality using these techniques was found to be 17 per cent and 19 per cent respectively. In a large proportion of cases identification of monoclonal lg components was predictive for the subsequent development of lymphoma. In the third part of the study the prevalence of lg heavy chain gene monoclonality was identified in a series of LSG biopsies from Japanese patients with SS using PCR and was found to be similar to that in the series of Western patients. Monoclonality of lg components was also examined in a series of 22 benign lymphoepithelial lesions (BLEL) from patients with SS using PCR, ISH and immunohistochemistry (IHC). Using these techniques B-cell monoclonality was identified in 17 of 22 lesions and in a proportion of cases preceded development of lymphoma elsewhere. Finally, in the last part of the study, the presence of the chromosome translocation t(14;18) was studied using the PCR in salivary gland tissues which showed monoclonality of lg components and in the extra-salivary gland lymphomas arising in these cases. This chromosome translocation was not identified in any of these cases, in keeping with lymphomas arising in other mucosa associated lymphoid tissues (MALT). Results from this study have shown that the earliest stages of a monoclonal lymphoproliferation can be identified using contemporary molecular biological techniques. In addition, these results clearly show the value of lg characterisation as a predictive tool for the development of lymphoma in SS and further our understanding of the generalised lymphoproliferation associated with the disease.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: The molecular pathology of Sjogren's syndrome. Applications to the prediction of early lymphoma
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Health and environmental sciences; Lymphoma
URI: https://discovery.ucl.ac.uk/id/eprint/10104717
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