Development Of Lymphoma In Patients Research Articles

14-3-3η Proteins as a Diagnostic Marker, Disease Activation Indicator, and Lymphoma Predictor in Patients with Primary Sjögren Syndrome.

Primary Sjögren syndrome (PSS) is a chronic, autoimmune, and lymphoproliferative disease of the connective tissue. In patients with PSS, the risk of developing B-cell non-Hodgkin lymphoma (NHL) increases dramatically, with a prevalence of approximately 5%. The 14-3-3 protein isoforms are phospho-serin/phospho-threonine binding proteins associated with many malignant diseases. This study aimed to evaluate the relationship between disease activity parameters and markers predicting lymphoma development in patients with PSS and 14-3-3η proteins. This study was designed as an analytical case-control study. A total of 57 PSS patients and 54 healthy volunteers were included in the study. The European League Against Rheumatism (EULAR) Sjögren syndrome disease activity index (ESSDAI) was used to assess systemic disease activity in PSS. Receiver operating characteristic (ROC) analysis was used to test the diagnostic accuracy measures of the analytical results. Multivariable linear regression analysis was used to evaluate the effects of independent variables on the 14-3-3η protein. The 14-3-3η protein serum levels were found to be significantly higher in PSS (2.72 [2.04-4.07]) than healthy controls (1.73 [1.41-2.43]) (P<0.0001). A significant relationship was found between 14-3-3η protein levels and ESSDAI group (β=0.385, 95%CI=0.318-1.651, P=0.005), hypocomplementemia (C3 or C4) (β=0.223, 95% CI=0.09-1.983, P=0.048) and purpura (β=0.252, 95% CI=0.335-4.903, P=0.022), which are accepted as lymphoma predictors. A significant correlation was found between PSS disease activity score ESSDAI and 14-33η protein (β=0.496, 95% CI=0.079-0.244, P=0.0002). 14-3-3η proteins are potential candidates for diagnostic marker, marker of disease activity, and predictor of lymphoma in PSS patients.

Radiomic Features Associated with Lymphoma Development in the Parotid Glands of Patients with Primary Sjögren’s Syndrome

Non-Hodgkin Lymphoma (NHL) represents a severe complication and the main cause of morbidity in patients with primary Sjögren's syndrome (pSS). This study aimed to assess the role of textural analysis (TA) in revealing lymphoma-associated imaging parameters in the parotid gland (PG) parenchyma of patients with pSS. This retrospective study included a total of 36 patients (54.93 ± 13.34 years old; 91.6% females) diagnosed with pSS according to the American College of Rheumatology and the European League Against Rheumatism criteria (24 subjects with pSS and no lymphomatous proliferation; 12 subjects with pSS and NHL development in the PG, confirmed by the histopathological analysis). All subjects underwent MR scanning between January 2018 and October 2022. The coronal STIR PROPELLER sequence was employed to segment PG and perform TA using the MaZda5 software. A total of 65 PGs underwent segmentation and texture feature extraction (48 PGs were included in the pSS control group, and 17 PGs were included in the pSS NHL group). Following parameter reduction techniques, univariate analysis, multivariate regression, and receiver operating characteristics (ROC) analysis, the following TA parameters proved to be independently associated with NHL development in pSS: CH4S6_Sum_Variance and CV4S6_Inverse_Difference_Moment, with an area under ROC of 0.800 and 0.875, respectively. The radiomic model (resulting by combining the two previously independent TA features), presented 94.12% sensitivity and 85.42% specificity in differentiating between the two studied groups, reaching the highest area under ROC of 0.931 for the chosen cutoff value of 1.556. This study suggests the potential role of radiomics in revealing new imaging biomarkers that might serve as useful predictors for lymphoma development in patients with pSS. Further research on multicentric cohorts is warranted to confirm the obtained results and the added benefit of TA in risk stratification for patients with pSS.

Determining the risk of developing EBV­-associated lymphoma in HIV-­infected patients

Objective — to increase the efficiency of predicting the development of EBV-associated lymphomas in patients with HIV infection.&#x0D; Materials and methods. In order to improve the prediction of the development of Epstein—Barr associated lymphomas in HIV-infected patients, a comparative analysis of various indicators (clinical-epidemiological, laboratory, serological, etc.) was carried out in 57 HIV patients who had clinical and laboratory confirmation of the presence of co-infection with the Epstein—Barr.Of the 57 patients, manifestations of primary CNS lymphoma were registered in 7 patients (12.3 %), another 1 patient was diagnosed with B-cell large cell lymphoma of the frontal sinus, centroblastic variant (1.8 %), in 1 patient — Burkitt’s lymphoma with lesions of the cervical lymph nodes (1.8 %). To clarify the main trends in the development of lymphomas in patients with HIV and EBV coinfection, a detailed analysis was carried out in two groups: the main group consisted of 9 patients with lymphomas, the remaining 48 patients without detected neoplasms formed the comparison group.&#x0D; Results and discussion. To improve the efficiency of the forecast, multifactorial logistic regressions were constructed, taking into account not only the independent, but also the joint influence of the considered risk factors. To do this, the sum of the scores for each observation was calculated using the corresponding predictive coefficient rank qualification created using the Wald analysis. Based on a multivariate prognostic model, an algorithm was created to determine the risk of developing EBV-associated lymphomas in patients co-infected with EBV and HIV.&#x0D; Conclusions.The created algorithm for determining the risk of developing EBV-associated lymphomas in patients with HIV makes it possible to identify patients with different risks of developing lymphomas under conditions of infection with EBV and HIV, which further creates the possibility for predicting an unfavorable course of HIV infection.The proposed algorithm has a high predictive efficiency, which makes it possible to determine the risk at the individual level and lays the foundation for optimizing the diagnosis of Epstein—Barr virus infection in HIV-infected patients.

Long-term exposure to monoclonal anti-TNF is associated with an increased risk of lymphoma in BAFF-transgenic mice.

The impact of treatment on the risk of lymphoma in patients with rheumatoid arthritis (RA) is unclear. Here, we aimed to assess if the risk of lymphoma differs according to the type of tumor necrosis factor inhibitor (TNFi), comparing monoclonal anti-TNF antibodies to the soluble TNF receptor. We used B cell activating factor belonging to the TNF family (BAFF)-transgenic (Tg) mice as a model of autoimmunity-associated lymphoma. Six-month-old BAFF-Tg mice were treated with TNFi for 12months. Histological examination of the spleen, assessment of the cellular composition of the spleen by flow cytometry and assessment of B cell clonality were performed at euthanasia. Crude mortality and incidence of lymphoma were significantly higher in mice treated with monoclonal anti-TNF antibodies compared to both controls and mice treated with the soluble TNF receptor, even at a high dose. Flow cytometry analysis revealed decreased splenic macrophage infiltration in mice treated with monoclonal anti-TNF antibodies. Overall, this study demonstrates, for the first time, that a very prolonged treatment with monoclonal anti-TNF antibodies increase the risk of lymphoma in B cell-driven autoimmunity. These data suggest a closer monitoring for lymphoma development in patients suffering from B cell-driven autoimmune disease with long-term exposure to monoclonal anti-TNF antibodies.

Leukocyte Immunoglobulin-Like Receptor A3 (LILRA3): A Novel Marker for Lymphoma Development among Patients with Young Onset Sjogren's Syndrome.

Background: Primary Sjogren’s syndrome (SS) is an autoimmune disease with a strong predilection for lymphoma development, with earlier disease onset being postulated as an independent risk factor for this complication. Variations of the Leukocyte immunoglobulin-like receptor A3 (LILRA3) gene have been previously shown to increase susceptibility for both SS and non-Hodgkin B-cell lymphoma (B-NHL) in the general population. We aimed to investigate whether variations of the LILRA3 gene could predispose for lymphoma development in the context of SS. Methods: Study population, all of Greek origin, included 101 SS cases with a current or previous diagnosis of lymphoma (SS-lymphoma, SS-L) and 301 primary SS patients not complicated by lymphoma (SS-non-lymphoma, SS-nL). All SS patients fulfilled the 2016 SS American College of Rheumatology/European league against Rheumatism (ACR/EULAR) classification criteria. A total of 381 healthy controls (HC) of similar age/sex/race distribution were also included. On the basis of the age of SS onset and the presence or absence of adverse predictors for lymphoma development, SS patients were further stratified into younger (≤40 years) and older (>40 years) age of disease onset, as well as into high/medium and low risk groups. Polymerase chain reaction (PCR) was implemented for the detection of the following LILRA3 gene variants: homozygous non-deleted or functional wild type (+/+) heterozygous (+/−) and homozygous deleted (−/−). LILRA3 serum protein levels were quantitated by enzyme-linked immunosorbent assay (ELISA) in 85 individuals (29 SS-L, 35 SS-nL patients and 21 HC). Results: While no statistically significant differences were detected in the overall frequency of LILRA3 gene variants between SS-L, SS-nL and HC groups, LILRA3 serum protein levels were increased in the SS-L group compared to HC (1.27 ± 1.34 vs. 0.38 ± 0.34 ng/mL, p-value: 0.004). After stratification according to the age of SS onset and history of lymphoma, as well as the presence or absence of adverse predictors for lymphoma development, the prevalence of the functional LILRA3 gene variant was found to be significantly increased in the young onset SS-L group compared to the HC of similar age and sex distribution (100% vs. 82.9%, p = 0.03), as well as in the high/medium risk SS compared to the low risk SS (91.3 vs. 78.3%, p = 0.0012). Of note, young onset SS-L and SS-nL groups displayed higher LILRA3 serum levels compared to their older counterparts (p-values: 0.007 and 0.0005, respectively). Conclusion: The functional LILRA3 gene variant increases susceptibility to SS-related lymphoma development in patients with a disease onset of <40 years old, implying that genetically determined deranged immune responses in younger SS individuals could underly their pronounced risk for lymphoma development.

Patients with autoimmune diseases have an altered activity of the PD-1 pathway and proportions of Epstein-Barr virus infected cells in benign lymphadenopathies

Patients with autoimmune diseases (AD) have an increased risk to develop benign lymphadenopathies compared to patients without AD. The aim with this study was to determine the role of the PD-1 pathway and the number of cells harboring Epstein-Barr virus (EBV) in benign lymphadenopathies in patients with AD (cases) compared to patients without AD (controls). Pathology registries were screened to identify patients with biopsies diagnosed as benign lymphadenopathy and medical journals were reviewed for information on AD. Immunohistochemical stainings (PD-1 and PD-L1) and EBER in situ hybridization for EBV were applied on lymph node biopsies in patients with AD (n = 22) and patients without AD (n = 57). The case group was compared with the control group with Wilcoxon-signed rank, chi-square and Fischeŕs exact test. There was a statistically significantly higher proportion of PD-1+ cells and a tendency for a lower prevalence of PD-L1+ and EBV+ cells in cases compared to controls. Apparently, patients with AD have an altered immune response as revealed in benign lymphadenopathies compared to patients without AD. If this association might be a piece of the puzzle for the increased risk of development of lymphomas in patients with AD remains to be determined.

Richter’s transformation in patients with chronic lymphocytic leukaemia: a Nationwide Epidemiological Study

Richter’s transformation (RT) refers to the development of an aggressive lymphoma in patients with chronic lymphocytic leukemia (CLL). Approximately, 2–10% of patients with CLL develop RT, most often as diffuse large B-cell lymphoma. To assess the incidence of RT, we examined risk factors for RT and death among patients with RT in a nationwide CLL cohort (from 2008 to 2016). Among 3772 patients, 113 had biopsy-proven RT. With a median follow-up of 4.3 years, the 5-year cumulative incidence of RT was 2.8%. Advanced Binet stage (B/C) (p<.001), unmutated IGHV (p<.001), and del(17p) (p<.001) were independently associated with risk of developing RT. Half of the patients with RT (49%) were treatment-naïve prior to transformation and demonstrated longer survival after RT compared to patients previously treated for CLL (6.1 vs. 2.8 years, p=.03). Whether this finding could be explained by a higher proportion of clonally unrelated RT among treatment-naïve patients, remain to be addressed.

Development of lymphoma in patients with primary Sjögren syndromes

Background: Lymphoma is the main complication of primary Sjogren syndrome (pSS). The aim of this study was to describe the prevalence and incidence rate of lymphoma in patients with pSS in eleven centers in Argentina. To determine the frequency of commitment of the domains of the baseline clinical ESSDAI in the patients who developed lymphoma in the course of their follow-up and compare it with the rest of the sample. Methods and findings: We included patients older than 18 years with a diagnosis of pSS according to American College of Rheumatology/European League against Rheumatism (ACR/EULAR)2002/2016 criteria, included in a multi-center Argentine database. Patients diagnosed with another associated autoimmune rheumatic disease were excluded. Six hundred and eighty one patients were included, 95% female, with a mean age of 54.41 years (± 13.70). Sixteen patients presented lymphoma (prevalence: 2.35%, 95% CI: 1.2-3.4%). The average follow-up time was 4.7 years (± 4.94). Six hundread and thirty three patients contributed data for the survival analysis. The incidence rate of lymphoma was 0.54 per 100 patient-years (95% CI: -0,26 a 1,34). The most frequently lymphoma type was MALT. Patients who developed lymphoma had a higher frequency of involvement of most of the domains of the baseline clinical ESSDAI compared to patients who did not present this complication, observing statistically significant differences in glandular (68,75% vs 28.69%, p:0,001), and cutaneous (31.25% vs 10.99%, p: 0.01) domains. The glandular domain of clinical ESSDAI was the main domain associated lymphoma development (H.R: 4.54, 95% CI: 1.57-13.12). Conclusion: This was the first study with data on the population of Argentina about the prevalence of lymphoma in patients diagnosed with Sjogren's syndrome. The prevalence of lymphoma in our cohort was lower than previously published. Despite observing a lower frequency of lymphoma in our study, we found an association with risk markers described in the literature, such as baseline parotidomegaly and cutaneous involvement.

Low miR200b-5p levels in minor salivary glands: a novel molecular marker predicting lymphoma development in patients with Sjögren’s syndrome

ObjectivesDevelopment of non-Hodgkin’s lymphoma (NHL) is the major adverse outcome of Sjögren’s syndrome (SS) affecting both morbidity and mortality. Preliminary evidence suggested that, although not deregulated compared with sicca controls,...

Prognostic value of cryoglobulins, protein electrophoresis, and serum immunoglobulins for lymphoma development in patients with Sjögren’s syndrome. A retrospective cohort study

Background: Patients with Sjögren’s syndrome (SS) have a considerable higher risk of lymphoma development.Objectives: To determine the incidence of lymphoma and the value of biomarkers to predict lymphoma development in patients with SS.Methods: Clinical files of all patients with a presumed diagnosis of SS between 1991 and 2016 were retrospectively reviewed for the development of lymphoma. Biochemical data were plotted as a function of the relative time before and after the lymphoma diagnosis (for patients who developed lymphoma) or before the last available blood test (for patients who did not develop lymphoma). Correlations between several biochemical parameters and development of lymphoma were analyzed by logistic regression. In order to evaluate the evolution of cryoglobulins, a random effect model with random intercepts was used.Results: Sixteen patients developed a lymphoma (prevalence 8.9%; median follow-up 6 years). Cryoglobulins were significantly higher in these patients (n = 16), when compared to the rest of patients (n = 164) without lymphoma (121 ± 250 versus 8 ± 24.9 mg/L for IgG; 231 ± 422 versus 13 ± 30 mg/L for IgM; 10 ± 20 versus 1 ± 4 mg/L for IgA in the cryoprecipitate). Cryoglobulin-levels were significantly more increasing (p-values for IgG = 0.0007; for IgM = 0.0123; and for IgA in the cryoprecipitate <0.0001) in the time period before the lymphoma diagnosis (patients with lymphoma) compared to the time period before the last available blood test (patients without lymphoma). Also low (i.e. under the detection limit) C3 (OR 13.9) or C4 (OR 7.1) levels, a progressively decreasing total complement activity (OR 6.6), progressively decreasing gammaglobulins (OR 13.4), a persistent detection of monoclonal bands (OR 14.6) on protein electrophoresis, a persistent low or decreasing serum IgG (OR 18), and decreasing IgM-serum levels (OR 17.7) were significantly associated with lymphoma.Conclusion: Periodically follow-up of laboratory markers, such as cryogloblins, over time proved to be an accurate way to predict lymphoma.

Rheumatoid Factor and Disease Activity Are Independent Predictors of Lymphoma in Primary Sjögren's Syndrome.

To define parameters predictive of lymphoma development in patients with primary Sjögren's syndrome (SS). A multicenter case-control survey was performed to identify predictors of lymphoma. Cases were patients who developed lymphoma after diagnosis of primary SS and were mainly recruited through the Club Rhumatismes et Inflammation network. For each case, 2 controls (matched for disease duration and age) were randomly selected among patients with primary SS and without lymphoma. Cases and controls were compared using univariate analysis and then using multivariate analysis to identify independent predictors of lymphoma. One hundred one patients with primary SS and lymphoma were included. Eighty-seven patients were women (86.1%), and the mean ± SD age at lymphoma diagnosis was 57.4 ± 12.6 years. The most frequent histologic type was B cell non-Hodgkin's lymphoma (NHL) in 99 of 101 patients, with marginal-zone lymphoma in 76 of the 99 patients (76.8%) including 58 (58.6%) with lymphoma of the mucosa-associated lymphoid tissue type. Lymphomas were most frequently located in the salivary glands (43 patients). A specific treatment was initiated at diagnosis in 87 patients with B cell NHL, and 61 patients (61.6%) achieved complete sustained remission after the first line of treatment. In the multivariate analysis, salivary gland enlargement, the presence of rheumatoid factor (RF), low C4, cryoglobulinemia, lymphopenia, and disease activity according to the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (excluding the lymphoma domain) were found to be predictors of lymphoma. No previous treatment for primary SS was associated with any effect on lymphoma occurrence. In addition to previously known factors predictive of lymphoma occurrence, the independent roles of RF and disease activity were demonstrated in this case-control study of primary SS-associated lymphoma. Our findings highlight the roles of chronic antigenic stimulation and disease activity in the development of this severe complication.

Review of Sjögren’s Syndrome for Primary Physicians

Sjogren`s syndrome is a chronic systemic autoimmune disease characterized by lymphocytic infiltration of the exocrine glands resulting in a dry mouth and eyes. The disease can present either alone or in association with other autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and inflammatory myopathy. In addition to symptoms caused by exocrinopathy, about half of patients present with extraglandular (systemic) manifestations including arthritis, Raynaud`s phenomenon, lymphadenopathy, vasculitis, peripheral neuropathy, and interstitial nephritis. Patients often suffer from severe fatigue, myalgia, and dryness, which lead to a poor quality of life. Physicians should be aware of the increased risk of lymphoma development in patients with Sjogren`s syndrome. Currently, there are no drugs available that are able to improve the natural course of disease, making symptom relief the primary goal of therapy. Currently, pilocarpine is the only drug clinically proven for the treatment of dry eyes and mouth in patients with Sjogren`s syndrome. (Korean J Med 2015;89:291-294)

Case control study to identify the risk factors for development of lymphoma in patients with hepatitis C infection.

e19519 Background: Multiple studies have demonstrated an increased risk of lymphoid malignancies in patients with hepatitis C infection. It is clear that not all patients with hepatitis C infection...

Sa1109 Meta-Analysis of Duration of Exposure to Thiopurines in Association With Development of Lymphoma in Patients With Inflammatory Bowel Disease

Sa1109 Meta-Analysis of Duration of Exposure to Thiopurines in Association With Development of Lymphoma in Patients With Inflammatory Bowel Disease

Artemis C-terminal region facilitates V(D)J recombination through its interactions with DNA Ligase IV and DNA-PKcs

Artemis is an endonuclease that opens coding hairpin ends during V(D)J recombination and has critical roles in postirradiation cell survival. A direct role for the C-terminal region of Artemis in V(D)J recombination has not been defined, despite the presence of immunodeficiency and lymphoma development in patients with deletions in this region. Here, we report that the Artemis C-terminal region directly interacts with the DNA-binding domain of Ligase IV, a DNA Ligase which plays essential roles in DNA repair and V(D)J recombination. The Artemis-Ligase IV interaction is specific and occurs independently of the presence of DNA and DNA-protein kinase catalytic subunit (DNA-PKcs), another protein known to interact with the Artemis C-terminal region. Point mutations in Artemis that disrupt its interaction with Ligase IV or DNA-PKcs reduce V(D)J recombination, and Artemis mutations that affect interactions with Ligase IV and DNA-PKcs show additive detrimental effects on coding joint formation. Signal joint formation remains unaffected. Our data reveal that the C-terminal region of Artemis influences V(D)J recombination through its interaction with both Ligase IV and DNA-PKcs.

Lymphoproliferative Lesions in IgG4-Related Disease

IgG4-related disease is a reactive lymphoproliferative-sclerosing lesion that can involve various organ systems of the body, with autoimmune pancreatitis being the prototype. This review article focuses on the various lymphoproliferative lesions that can occur in this disease. The first is IgG4-related lymphadenopathy, which can accompany typical IgG4-related disease or occur ab initio. The morphologic spectrum of the affected lymph nodes ranges from multicentric Castleman disease-like, to follicular hyperplasia, marked interfollicular expansion mimicking peripheral T-cell lymphoma, progressive transformation of germinal center-like, and nodal inflammatory pseudotumor-like. The diagnosis can be confirmed by demonstration of an increase in IgG4+ plasma cells. The second is the development of lymphoma in patients with IgG4-related disease. The lymphoma can occur in the sites affected by IgG4-related disease, where the most common type is extranodal marginal zone lymphoma; or in other nodal and extranodal sites, where the most common type is diffuse large B-cell lymphoma. The third is florid lymphoid hyperplasia as the dominant morphologic feature of IgG4-related disease in various extranodal sites, mimicking malignant lymphoma. Such findings appear to be particularly common in the salivary gland, lacrimal gland, skin and breast, probably attributable to early discovery of mass lesions involving these sites, before the sclerosing process has time to take over. Keywords: IgG4-related disease, IgG4-related sclerosing disease, lymphoproliferative lesion, pseudolymphoma, lymph node pathology, lymphadenopathy, lymphoma, florid lymphoid hyperplasia, follicular hyperplasia, Castleman disease-like

TNFα antagonist therapy does not increase the Epstein-Barr virus burden in patients with rheumatoid arthritis or ankylosing spondylitis

ObjectiveThe risk of non-Hodgkin lymphoma is increased in rheumatoid arthritis (RA) but not in ankylosing spondylitis (AS). In RA, the degree of inflammation is closely associated with the lymphoma risk. Whether immunosuppressants such as methotrexate and TNFα antagonists affect the lymphoma risk in RA is unclear. The Epstein-Barr virus (EBV) may contribute to the pathogenesis of RA and may be involved in the development of lymphoma in patients taking methotrexate and/or TNFα antagonists, although these points remain debated. EBV load monitoring during immunosuppressive treatment may predict the occurrence of EBV-related lymphoma. Here, our objective was to prospectively measure the EBV load in patients receiving TNFα antagonists for RA or AS. MethodsWe prospectively studied patients with RA or AS before and after TNFα antagonist therapy initiation. The EBV load was measured in blood samples using the EBV R-gene Quantification Kit. Disease activity at the time of blood sampling was evaluated by determining the Disease Activity Score 28 (DAS28) in RA patients and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in AS patients. ResultsWe included 46 patients with RA (82.6% women; mean age, 52.7±11.3 years) and 27 with AS (men, 81.5%; mean age, 45.1±12.7 years). In the RA group, the EBV load was measured at baseline and 9.72±5.7 months later. The baseline EBV load was undetectable in 33 (70.2%) patients; mean EBV load in the 13 remaining patients was 9389copies/ml (3.47 log10±0.45). Baseline EBV load did not correlate with disease activity (DAS28). At the follow-up assay, the EBV load became positive in five patients and increased significantly in one patient (four patients on etanercept, one on adalimumab, and one on infliximab); it became negative in six patients (five on adalimumab and one on etanercept) and showed non-significant changes in six patients. Mean EBV load in patients positive at follow-up was 3.63±0.52 log10 copies/ml. Mean DAS28 was 4.78±1.1 at baseline and 2.94±1.24 at follow-up. At follow-up, a good EULAR response was noted in 33 (71.7%) patients and a moderate EULAR response in seven (15.2%) patients. In the AS group, the baseline EBV load measurement occurred after 12.9±10.6 months. Baseline EBV load was undetectable in 25 (92.6%) patients; mean load in the remaining two patients was 4.15±0.46 log10 copies/ml. At follow-up, the EBV load became positive in two patients (one on adalimumab and one on infliximab) and became negative in one patient (on adalimumab). Mean load in positive patients was 3.33±0.24 log10 copies/ml. Mean BASDAI was 55.1±16.2 at baseline and 17.88±18.62 at follow-up. A positive EBV load was significantly more common in the RA group than in the AS group (P=0.039). EBV load changes did not differ significantly between the RA and AS groups or across TNFα antagonists. No cases of lymphoma were recorded. ConclusionIntroducing TNFα antagonist therapy does not affect the EBV load in patients with RA or AS. EBV load monitoring is probably unnecessary in patients given TNFα antagonists for RA or AS.

85 Risk of non-Hodgkin lymphoma development in patients carrying mutations in CHEK2 gene or polymorphism R72P in P53 gene

85 Risk of non-Hodgkin lymphoma development in patients carrying mutations in CHEK2 gene or polymorphism R72P in P53 gene

Epstein-Barr Virus (EBV) Prevalence and the Risk of Reactivation in Patients with Inflammatory Arthritis Using Anti-TNF Agents and in those who are Biologic Naive

Objective:Anti-TNF agents (etanercept, infliximab and adalimumab) are widely used in inflammatory conditions, such as rheumatoid arthritis; however, they are not without side effects, potentially including lymphoma. We compared Epstein-Barr virus (EBV) levels in patients with inflammatory arthritis taking biologic agents and controls matched for disease, age, gender and disease duration who were biologic naïve. Secondly, we determined the risk of reactivation of EBV in patients taking biologics.Methods:One hundred and twenty-two patients were recruited and blood samples were collected. Immunoglobulin G (IgG) antibody to EBV was analysed using enzyme-linked immunosorbent assay. EBV DNA was analysed using polymerase chain reaction (PCR) on all positive IgG samples. Quantitative measures of viral DNA were made and expressed as copies/reaction volume. Reactivation was defined as the presence of viral DNA in the plasma and PCR activity was evaluated between 6 and 18 months after anti-TNF therapy.Results:IgG for EBV was detected in 98% of controls and 90% of cases. Viral reactivation related to EBV was not observed in this study. There was one patient who tested positive for EBV using PCR, but upon confirmatory testing, this sample was actually negative. No samples were positive on PCR at the follow-up time points.Conclusion:There was a high rate of EBV IgG in the cases and controls in this study. Given the small sample size and timeframe for this study, treatment with anti-TNF agents does not seem to lead to EBV reactivation, and thus, this is likely not a mechanism for the development of lymphoma in patients taking biologics.

Chronic lymphocytic leukemia with paraimmunoblastic transformation – with comparative genomic hybridization and review of the literature

Richter's transformation (RT) is the development of a high-grade lymphoma in patients with B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). We report an extremely rare case with paraimmunoblastic transformation. A 78-year-old Taiwanese male had Rai stage 1 and Binet stage B CLL/SLL involving skin, peripheral blood (PB), and bone marrow (BM) with paraimmunoblastic transformation in the lymph node. Molecular/genomic studies showed the same clonal origin of tumor tissues at various locations with trisomy 12 and a deletion of chromosome 13q14. Interestingly, there seemed to be no additional chromosomal aberrations in the transformed nodal tissue, suggesting that the micro-environment rather than an additional genetic lesion contributed to the transformation. The patient received chemotherapy and was alive with disease after 33.5 months.