Defective repair of O6-methylguanine-DNA in primary Sjogren's syndrome patients predisposed to lymphoma.

Guo, K.; Major, Glenn N.; Foster, Hamish McA.; Bassendine, MF; Collier, Jane; Росс, Д. В.; Griffiths, I. D.

doi:10.1136/ard.54.3.229

Cited by 30 publications

(14 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Apoptosis can be viewed as the ultimate cellular stress response chosen by severely damaged cells, whereas a milder form of stress is met by the cell with a recovery attempt, including DNA repair. An abnormality in such a recovery process is suggested by reports of DNA repair alterations in SLE and Sjögren's syndrome patients (2,11,12,19) and by our observation of an enhanced cell cycle arrest in gamma-irradiated Sjögren's syndrome lymphocytes (G. Henriksson et al, submitted for publication). An interesting report of the SSB autoantigen showing promoter gene switching and alternative splicing specific for a Sjögren's syndrome patient also indicates a primary defect in the antigenic targets of ANA (32).…”

Section: Discussionmentioning

confidence: 73%

“…Instead, experimental data and some hypotheses for the pathogenesis of systemic autoimmune disease fit a more general origin of ANA, including DNA damage, its cellular repair, and the eventual stress situation of apoptosis. Abnormalities in DNA repair have been documented in SLE (2,12) and Sjögren's syndrome (11,19), as well as low-rate generation in Sjögren's syndrome patients of chromosome translocations linked to illegitimate V(D)J recombination (13). Hypotheses include those of Harris et al (12), postulating defective DNA repair as an autoimmunity susceptibility factor, and Fox et al (9), suggesting an abnormal processing of immunoglobulin and T-cell receptor genes as a basic pathogenetic phenomenon, as well as that of Tak et al (28), with a scenario of hyperproduction of reactive oxygen species in chronic inflammation, leading to DNA strand breakage, p53 accumulation, and p53 mutation.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Exposure of HEp-2 Cells to Stress Conditions Influences Antinuclear Antibody Reactivity

Du¹,

Fukushima²,

Sallmyr³

et al. 2002

Clin Vaccine Immunol

View full text Add to dashboard Cite

This study of stress-related antinuclear antibody (ANA) reactivity was undertaken with the objective of improving clinical ANA testing. ANA was determined by parallel enzyme-linked immunosorbent assays of crude nuclear protein antigen extracted from HEp-2 cells either grown under optimal conditions (providing nonstress ANA antigen) or exposed to stress (providing stress ANA antigen). The stress stimuli used were gamma radiation (causing DNA damage) and a hypertonic environment (causing apoptosis). Signs of stress-related ANA reactivity were seen among connective tissue disease (CTD) patients (including patients with systemic lupus erythematosus; mixed CTD; calcinosis, Reynaud's phenomenon, esophageal motility disorders, sclerodactyly, and telangiectasia; scleroderma; and Sjögren's syndrome): 11% showed stress-positive ANA (i.e., a significantly stronger ANA reactivity with the extract from stressed cells), whereas 21% showed a markedly weaker reaction with the stress antigen. In contrast, among ANA screening patient sera, with no diagnosis of CTD, the fraction showing stress-positive ANA was higher (7 to 8%, depending on the type of stress) than among those showing a lower reactivity with stress antigen (1.5 to 2.5%). Only one serum among 89 (1%) tested sera from healthy individuals showed a stress-related ANA reaction. This demonstration of stress-related ANA suggests a means to improve the performance of clinical ANA testing.

show abstract

Section: Discussionmentioning

confidence: 73%

mentioning

confidence: 99%

Exposure of HEp-2 Cells to Stress Conditions Influences Antinuclear Antibody Reactivity

Du¹,

Fukushima²,

Sallmyr³

et al. 2002

Clin Vaccine Immunol

View full text Add to dashboard Cite

show abstract

“…In the neoplastic process the cytokine network is unbalanced in favor of a Th2 pattern, while in salivary lymphoepithelial lesions the Th1 pattern prevails [34, 35]. Moreover, in lymphocyte extracts of SS patients with parotid enlargement, a lower level of the enzyme O 6 -methylguanine-DNA methyltransferase has been found compared to SS patients without parotidomegaly; this alteration causes defective DNA repairing which may favor lymphoma development [36]. In some caes of NHL associated with SS, t(14;18), a typical translocation of follicular lymphomas, was found, but only after lymphoma onset; this translocation increases the production of bcl-2 protein, which is able to inhibit apoptosis [37].…”

Section: Introductionmentioning

confidence: 99%

Mucosa-Associated Lymphoid Tissue Lymphoma of the Salivary Glands Occurring in Patients Affected by Sjögren’s Syndrome: Report of 6 Cases

Biasi¹,

Caramaschi²,

Ambrosetti³

et al. 2001

Acta Haematol

View full text Add to dashboard Cite

Objective: Mucosa-associated lymphoid tissue (MALT) lymphoma of the salivary glands occurring in 6 patients affected by primary Sjögren’s syndrome is reported. Methods: Clinical findings, histologic type, stage, treatment and outcome of the 6 patients have been revised. Results: In all 6 cases the lymphoma was of the MALT type. Four patients had stage IE disease, 1 patient had stage IIE disease and 1 patient had stage IV disease. The patients received different treatments resulting in all cases in prolonged remission. After 7 years of complete remission 1 patient developed a diffuse large B-cell lymphoma. Conclusion: MALT lymphoma of the salivary glands is an indolent disease. Though the best therapy of this lymphoproliferative disorder remains to be established, prolonged remission has been obtained in our cases with different therapeutic approaches. We review the literature regarding the relationship between Sjögren’s syndrome and MALT lymphomas and study the mechanisms which may be involved in the transformation from a lymphoepithelial lesion into a neoplastic disorder.

show abstract

“…Moreover, the frequency of the classical t(11;18) (q21;q21) translocation was much lower in SS patients with extra gastrointestinal than with gastric MALT lymphomas [90]. Evidence of defective repair of a pro-mutagenic DNA base lesion, O6-methylguanine, has been observed in the lymphocytes of patients with pSS predisposed to lymphoma [91], suggesting that these patients may have defective DNA repair mechanisms. Other genetic events, such as bcl-2 or c-Myc amplification, trisomy 3 or 18, may facilitate the progression of low-grade MALT lymphoma to a more malignant high-grade lymphoma [43, 48, 64, 91, 92].…”

Section: Oncogene Molecules and Othersmentioning

confidence: 99%

“…Evidence of defective repair of a pro-mutagenic DNA base lesion, O6-methylguanine, has been observed in the lymphocytes of patients with pSS predisposed to lymphoma [91], suggesting that these patients may have defective DNA repair mechanisms. Other genetic events, such as bcl-2 or c-Myc amplification, trisomy 3 or 18, may facilitate the progression of low-grade MALT lymphoma to a more malignant high-grade lymphoma [43, 48, 64, 91, 92]. Activation of the enzyme cytidine deaminase (AID) has been associated with somatic hypermutation and class switch recombination [65].…”

Section: Oncogene Molecules and Othersmentioning

confidence: 99%

Possible Mechanisms of Lymphoma Development in Sjogren’s Syndrome

Dong¹,

Chen²,

Yasukawa³

et al. 2013

CIR

View full text Add to dashboard Cite

Primary Sjögren’s syndrome (pSS) is a systemic as well as an organ-specific autoimmune disease characterized by lymphocytic infiltration of the glandular epithelial tissue. SS patients have been reported to be at highest risk of developing lymphoproliferative neoplasms, when compared with patients with other rheumatoid diseases. Factors such as cytokine stimulation, environmental factors, viral infection and genetic events as well as vitamin deficiency may contribute to the development of lymphoma. Over the past few decades, numerous efforts have been made to assess the relationship between lymphoma and SS. These include epidemiological surveys, molecular biologic assessments of clonality and well-linked register cohort studies evaluating the predictive value of clinical, laboratory and histological findings. Nevertheless, the mechanisms and factors predictive of lymphoma development in pSS patients remain to be defined. This review summarizes updated knowledge on the incidence of and risk factors for lymphoma development in pSS patients, as well as discussing the most recent findings on the development and treatment of lymphoma in pSS patients and the possible mechanism of lymphoma development.

show abstract

Defective repair of O6-methylguanine-DNA in primary Sjogren's syndrome patients predisposed to lymphoma.

Cited by 30 publications

References 11 publications

Exposure of HEp-2 Cells to Stress Conditions Influences Antinuclear Antibody Reactivity

Exposure of HEp-2 Cells to Stress Conditions Influences Antinuclear Antibody Reactivity

Mucosa-Associated Lymphoid Tissue Lymphoma of the Salivary Glands Occurring in Patients Affected by Sjögren’s Syndrome: Report of 6 Cases

Possible Mechanisms of Lymphoma Development in Sjogren’s Syndrome

Contact Info

Product

Resources

About