Prolonged response after TPO-RA discontinuation in primary ITP: results of a prospective multicenter study.

Sustained response off treatment (SROT) after thrombopoietin receptor agonist (TPO-RA) discontinuation has been reported in immune thrombocytopenia (ITP). This prospective multicenter interventional study enrolled adults with persistent or chronic primary ITP and complete response (CR) on TPO-RAs. The primary end point was the proportion of patients achieving SROT (platelet count >30 × 109/L and no bleeding) at week 24 (W24) with no other ITP-specific medications. Secondary end points included the proportion of sustained CR off-treatment (SCROT, platelet count >100 × 109/L and no bleeding) and SROT at W52, bleeding events, and pattern of response to a new course of TPO-RAs. We included 48 patients with a median age of 58.5 years; 30 of 48 had chronic ITP at TPO-RA initiation. In the intention-to-treat analysis, 27 of 48 achieved SROT, 15 of 48 achieved SCROT at W24; 25 of 48 achieved SROT, and 14 of 48 achieved SCROT at W52. No severe bleeding episode occurred in patients who relapsed. Among patients rechallenged with TPO-RA, 11 of 12 achieved CR. We found no significant clinical predictors of SROT at W24. Single-cell RNA sequencing revealed enrichment of a tumor necrosis factor α signaling via NF-κB signature in CD8+ T cells of patients with no sustained response after TPO-RA discontinuation, which was further confirmed by a significant overexpression of CD69 on CD8+ T cells at baseline in these patients as compared with those achieving SCROT/SROT. Our results strongly support a strategy based on progressive tapering and discontinuation of TPO-RAs for patients with chronic ITP who achieved a stable CR on treatment. This trial was registered at www.clinicaltrials.gov as #NCT03119974.

Systemic lupus erythematosus associated with HIV infection: a retrospective case-control study.

OBJECTIVES: The association of systemic lupus erythematosus (SLE) and human immunodeficiency virus (HIV) remains scarcely described in the literature. Our objectives were to describe the characteristics of SLE in patients living with HIV (SLE-PLHIV) and compare it with SLE characteristics in patients without HIV infection. METHODS: We performed a retrospective study of 13 patients with SLE-PLHIV diagnosed between 1975 and 2020 in four different French hospitals. These patients were compared in a case-control study with a 1:5 ratio to age-, sex- and year of diagnosis- matched patients with SLE without HIV infection. RESULTS: Median (IQR) age at SLE diagnosis for patients with SLE and HIV infection was 43 years (36-53). There were 77% women. Main clinical manifestations were polyarthrtitis (84%), cutaneous lupus (69%), kidney disease (54%), serositis (15%) and autoimmune cytopenias (auto-immune haemolytic anaemia and/or immune thrombocytopenia) (31%). There were no neuropsychiatric manifestations. All patients had positive antinuclear antibody test with a titre ≥1:160. Anti-dsDNA antibodies were present in 75% of patients, and anti-Sm antibodies in 33%. SLE-PLHIV had more frequently renal manifestations (54 vs. 16%, p=0.006) and autoimmune cytopenia (31 vs 8%, p=0.04) than patients without HIV infection. CONCLUSIONS: SLE and HIV infection appear to be a rare association. Patients with SLE-PLHIV seem to have more renal manifestations and autoimmune cytopenias than patients with SLE without HIV infection.

Hemophagocytic Lymphohistiocytosis Associated With Cytomegalovirus Infection: 5 Cases and a Systematic Review of the Literature.

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disorder characterized by an uncontrolled, persistent, hyperimmune response. It can be triggered by an infectious, neoplastic, or autoimmune event. The involvement of cytomegalovirus (CMV) in the onset of HLH is subject to debate, and the epidemiology of CMV-associated HLH (HLH-CMV) remains poorly characterized. We identified 5 cases of HLH-CMV in our hospital, systematically searched the PubMed database for publications on HLH-CMV, and reviewed 57 publications with a total of 67 cases of HLH-CMV. Only 48 patients (71.6%) were immunodeficient, suggesting that HLH-CMV can occur in immunocompetent patients. The major cause of underlying immunodepression (51%) was inflammatory bowel disease (mainly treated with azathioprine). CMV infection was nearly always symptomatic, and lung involvement was frequent (31 cases). Fifty-five patients recovered. Nineteen patients were treated for CMV infection only and had a good outcome, suggesting that antiviral drugs might be the cornerstone of HLH-CMV treatment.

Paraneoplastic pemphigus uncovers distinct clinical and biological phenotypes of western unicentric Castleman disease.

Unicentric Castleman disease (UCD) is a lymphoproliferative disease of unknown cause. Paraneoplastic pemphigus (PNP) is a major complication shown to be associated with a poor prognosis, with particular severity in patients with bronchiolitis obliterans (BO). This study describes the clinical and biological characteristics of UCD-PNP patients in a large Western cohort. A total of 148 patients diagnosed with UCD were identified, including 14 patients with a defined PNP. PNP was significantly associated with myasthenia gravis (MG) and FDC sarcoma during follow-up (FDCS). PNP was also significantly associated with reduced survival. These data, together with a multivariate analysis by principal components, led to the identification of UCD-PNP as a group at risk of MG, FDCS and death. PDGFRB sequencing performed on UCD lesions from six patients found the gain-of-function p.N666S variant in two. Interestingly, both patients had hyaline-vascular UCD subtype, were in the UCD-PNP subgroup and had FDCS. Sera from 25 UCD-PNP patients and 6 PNP patients without UCD were tested for PNP-associated autoantibodies. Sera from UCD-PNP patients had a strong reactivity against the N-terminal domain of recombinant periplakin (rPPL, 82%) and showed reactivity against at least two domains of rPPL. These features were not found in patients with UCD alone or in the PNP group without UCD. These data indicate that UCD-PNP patients belong to a subgroup sharing strong clinical and biological identity that might help to decipher the different dynamics of UCD natural history.

Lymphoma as an Exclusion Criteria for CVID Diagnosis Revisited.

PURPOSE: Hypogammaglobulinemia in a context of lymphoma is usually considered as secondary and prior lymphoma remains an exclusion criterion for a common variable immunodeficiency (CVID) diagnosis. We hypothesized that lymphoma could be the revealing symptom of an underlying primary immunodeficiency (PID), challenging the distinction between primary and secondary hypogammaglobulinemia. METHODS: Within a French cohort of adult patients with hypogammaglobulinemia, patients who developed a lymphoma either during follow-up or before the diagnosis of hypogammaglobulinemia were identified. These two chronology groups were then compared. For patients without previous genetic diagnosis, a targeted next-generation sequencing of 300 PID-associated genes was performed. RESULTS: A total of forty-seven patients had developed 54 distinct lymphomas: non-Hodgkin B cell lymphoma (67%), Hodgkin lymphoma (26%), and T cell lymphoma (7%). In 25 patients, lymphoma developed prior to the diagnosis of hypogammaglobulinemia. In this group of patients, Hodgkin lymphoma was overrepresented compared to the group of patients in whom lymphoma occurred during follow-up (48% versus 9%), whereas MALT lymphoma was absent (0 versus 32%). Despite the histopathological differences, both groups presented with similar characteristics in terms of age at hypogammaglobulinemia diagnosis, consanguinity rate, or severe T cell defect. Overall, genetic analyses identified a molecular diagnosis in 10/47 patients (21%), distributed in both groups and without peculiar gene recurrence. Most of these patients presented with a late onset combined immunodeficiency (LOCID) phenotype. CONCLUSION: Prior or concomitant lymphoma should not be used as an exclusion criteria for CVID diagnosis, and these patients should be investigated accordingly.

A regimen with caplacizumab, immunosuppression, and plasma exchange prevents unfavorable outcomes in immune-mediated TTP.

The anti-von Willebrand factor nanobody caplacizumab was licensed for adults with immune-mediated thrombotic thrombocytopenic purpura (iTTP) based on prospective controlled trials. However, few data are available on postmarketing surveillance. We treated 90 iTTP patients with a compassionate frontline triplet regimen associating therapeutic plasma exchange (TPE), immunosuppression with corticosteroids and rituximab, and caplacizumab. Outcomes were compared with 180 historical patients treated with the standard frontline treatment (TPE and corticosteroids, with rituximab as salvage therapy). The primary outcome was a composite of refractoriness and death within 30 days since diagnosis. Key secondary outcomes were exacerbations, time to platelet count recovery, the number of TPE, and the volume of plasma required to achieve durable remission. The percentage of patients in the triplet regimen with the composite primary outcome was 2.2% vs 12.2% in historical patients (P = .01). One elderly patient in the triplet regimen died of pulmonary embolism. Patients from this cohort experienced less exacerbations (3.4% vs 44%, P < .01); they recovered durable platelet count 1.8 times faster than historical patients (95% confidence interval, 1.41-2.36; P < .01), with fewer TPE sessions and lower plasma volumes (P < .01 both). The number of days in hospital was 41% lower in the triplet regimen than in the historical cohort (13 vs 22 days; P < .01). Caplacizumab-related adverse events occurred in 46 patients (51%), including 13 major or clinically relevant nonmajor hemorrhagic events. Associating caplacizumab to TPE and immunosuppression, by addressing the 3 processes of iTTP pathophysiology, prevents unfavorable outcomes and alleviates the burden of care.

Real-life use of mTOR inhibitor-based therapy in adults with autoimmune cytopenia highlights strong efficacy in relapsing/refractory multi-lineage autoimmune cytopenia.

Data on mTOR inhibitors (mTORi) in autoimmune cytopenia (AIC), in adults are scarce. We retrospectively analysed 30 cases of refractory or relapsing AIC treated with an mTORi-based therapy. Eleven warm autoimmune hemolytic anaemia, 10 autoimmune thrombocytopenia, 6 acquired pure red cell aplasia, 3 autoimmune neutropenia were included. Twenty were multilineage AIC (67%) and 21 were secondary AIC (70%). mTORi were associated with other therapies in 23 AIC (77%). Twenty-two AIC (73%) responded to mTORi-based therapy: 5 reached a partial response (17%) and 17 a complete response (57%). Survival without unfavourable outcome (failure, requirement of a new therapy, or death) was longer in multilineage AIC compared to single-lineage AIC (p = 0.049) with a median event-free survival of 48 versus 12 months. Median event-free survival was 48 months in secondary AIC and 33 months in primary AIC (p = 0.79). mTORi were discontinued in 4 patients (15%) for safety reasons and in 3 patients for patient's choice (12%). In conclusion, mTORi could be considered as an alternative or an add-on therapy in refractory or relapsing AIC in adult patients, especially in multilineage AIC.

Preemptive cyclosporin A in immune-mediated thrombotic thrombocytopenic purpura.

Survivors of immune-mediated thrombotic thrombocytopenic purpura (iTTP) are exposed to clinical relapses when a disintegrin and metalloproteinase with thrombospondin type 1 repeats, member 13 (ADAMTS13) activity decreases during follow-up. Although preemptive rituximab usually improves ADAMTS13 activity in this context, 15% of patients experience refractoriness or intolerance to rituximab and require alternative strategies. Here, we addressed whether cyclosporine A (CSA) could improve ADAMTS13 activity and prevent clinical relapses in this context. We treated preemptively with CSA 14 iTTP patients who were unresponsive (n = 11) or intolerant (n = 3) to rituximab. All patients had a severe ADAMTS13 deficiency (activity <20%) and otherwise in clinical remission. ADAMTS13 activity normalized in almost all patients (n = 13, 93%), after a median time of 2.5 months [IQR 1-6] following initiation. Median duration of CSA treatment was 17.5 months [IQR 10-34]. ADAMTS13 activity further declined to undetectable values during follow-up in five patients, but retreatment with rituximab or CSA allowed a recovery in ADAMTS13 activity in three cases. CSA could be stopped durably in two patients, while two others experienced an ADAMTS13 relapse. Severe but reversible side effects requiring cessation of the treatment occurred in two patients. CSA provides high and sustained response rates in patients who are refractory or intolerant to rituximab, with acceptable adverse events.

Efficacy and safety of two rituximab biosimilars for treating immune thrombocytopenia: a reference-product matched study.

The emergence of rituximab biosimilars offers the prospect of significant savings to the healthcare system. However, these drugs have never been evaluated for treating immune thrombocytopenia (ITP). This was an observational, matched study. We included adults who received a rituximab biosimilar for ITP. Each rituximab-naïve biosimilar patient was matched with two controls from the historic ITP-ritux registry. For non-naïve patients, we compared the response to the biosimilar with that observed with the reference product. Response status was defined according to international criteria. We included 107 patients; 55 receiving Rixathon™ and 52 Truxima™. Three months after the first infusion of rituximab biosimilars, the overall response rate was 47/74 (63.5%) versus 76/142 (53.5%) for the matched controls receiving the reference product (p = .13). The 3-month overall response rate was 76.5% for Rixathon™ versus 51.5% for the matched control group (p = .01) and 21/40 (52.5%) for Truxima™ versus 41/74 (55.4%) for the matched controls (p = .81). For non-naïve patients, the response pattern was similar to that observed previously with the reference product. Safety was analogous to that observed with the reference product. Rituximab biosimilars seemed safe and effective for ITP treatment.

What is the context? Immune thrombocytopenia (ITP) is an autoimmune disease defined by a low platelet count without any other cause of thrombocytopenia. Patients with ITP may experience severe bleedings.Rituximab, a biotechnological therapy, is a valid second-line treatment option for ITP.Biotechnological therapies are expensive. Because the patent expiratory date of the reference product of Rituximab expired, highly similar drugs called biosimilars have been developed and used in ITP treatment without any direct evaluation in this particular disease.What is new? In this study, we evaluate the efficacy and safety of rituximab biosimilars versus the reference product for treating adult ITPWe included adults who received a rituximab biosimilar for ITP. Each rituximab-naïve biosimilar patient was matched with two controls from a historic registry that included ITP patients treated by the reference product. For non-naïve patients, we compared the response to the biosimilar with that observed with the reference product.For naïve and non-naïve patients, the response pattern was similar to that observed previously with the reference product. Safety was analogous to that observed with the reference product.What is the impact? This study provides further evidence that rituximab biosimilars are safe and effective for immune thrombocytopenia treatment.

Characteristics of thrombocytopenia, anasarca, fever, reticulin fibrosis and organomegaly syndrome: a retrospective study from a large Western cohort.

Idiopathic multicentric Castleman disease (iMCD) is a non-clonal inflammatory lymphoproliferative disorder of unknown origin. Recently, TAFRO syndrome (thrombocytopenia, anasarca, fever, reticulin fibrosis and organomegaly) emerged as a singular variant of iMCD in Asia and was associated with a severe course and a poor outcome. The present study describes the first large Western cohort of TAFRO syndrome patients (n = 25) meeting the All Japan TAFRO Syndrome Research Group diagnostic criteria. Characteristics of TAFRO patients were compared to iMCD-not otherwise specified (iMCD-NOS) patients used as a control group (n = 43). Our results show that despite baseline characteristics in accordance with previously reported series, Western TAFRO syndrome patients do not appear to present with a worse outcome than iMCD-NOS patients. There were no significant differences between the two groups regarding treatment choice, response to rituximab (71% vs. 67%) or tocilizumab (69% vs. 91%) in TAFRO and iMCD-NOS, respectively. The two-year overall survival was above 95% in both groups. Limits of inclusion and exclusion criteria for TAFRO definition are also discussed. Our findings raise the question of the singularity of the TAFRO entity in Western countries. The data should promote further research using unsupervised models to identify markers of disease severity in Western cohorts of iMCD patients.

Hepatic haemophagocytosis in haematology patients with hepatic dysfunction: prognostic impact and contribution of liver biopsy combined with the haemophagocytic syndrome diagnostic score (HScore).

Hepatic dysfunction (HD) is common in patients with haematological malignancies. Hepatic haemophagocytosis (HH) was detected in >50% of liver biopsies taken when HD remained unresolved after standard examination. We aimed to explore the contribution of liver biopsy in patients with both haematological malignancies and HD, describe the population of patients with HH, assess the prognostic impact of HH, and investigate haemophagocytic syndrome diagnostic score (HScore) utility in patients with HH. Between 2016 and 2019, 116 consecutive liver biopsies (76 transjugular, 40 percutaneous) were taken in 110 patients with haematological malignancy and HD (hyperbilirubinaemia, elevated transaminases, and/or cholestasis) and without a clear diagnosis. Liver biopsies were safe and diagnostically efficient. Predominant diagnoses included: HH (56%), graft-versus-host disease (55%), associated infections (24%), sinusoidal obstruction syndrome (15%), and tumoral infiltration (8%). Of patients, 35% were critically ill and 74% were allogeneic haematopoietic stem cell transplantation recipients, while 1-year overall survival (OS) was 35% with HH versus 58% without HH (p = 0.026). The 1-year OS was 24% with a HScore of ≥169 versus 50% with a HScore of <169 (p = 0.019). Liver biopsies are feasible in and contribute significantly to haematology patients with HD. HH occurred frequently and was associated with a poor prognosis. Combined with liver biopsy, the HScore may be helpful in refining haemophagocytic syndrome diagnosis.

Clonal haematopoiesis of indeterminate potential and cardiovascular events in systemic lupus erythematosus (HEMATOPLUS study).

OBJECTIVE: The detection of somatic mutations among the genes of myeloid cells in asymptomatic patients-defining clonal haematopoiesis of indeterminate potential (CHIP)-is associated with a predisposition to cardiovascular events (CVEs) in the general population. We aimed to determine whether CHIP was associated with CVEs in SLE patients. METHODS: The study is an ancillary study of the randomized, double-blind, placebo-controlled, multicentre PLUS trial conducted from June 2007 through August 2010 at 37 centres in France, involving 573 SLE patients. The search for somatic mutations by high-throughput sequencing of 53 genes involved in clonal haematopoiesis was performed on genomic DNA collected at PLUS inclusion. CHIP prevalence was assessed in SLE and in a retrospective cohort of 479 patients free of haematological malignancy. The primary outcome was an incident CVE in SLE. RESULTS: Screening for CHIP was performed in 438 SLE patients [38 (29-47) years, 91.8% female]. Overall, 63 somatic mutations were identified in 47 patients, defining a CHIP prevalence of 10.7% in SLE. Most SLE patients (78.7%) carried a single mutation. Most variants (62.5%) were located in the DNMT3A gene. CHIP frequency was related to age and to age at SLE diagnosis, and was associated with a lower frequency of aPLs. CHIP occurred >20 years earlier (P < 0.00001) in SLE than in controls. The detection of CHIP at inclusion was not found to be associated with occurrence of CVEs during follow-up [HR = 0.42 (0.06-3.21), P = 0.406]. CONCLUSION: The prevalence of CHIP is relatively high in SLE for a given age, but was not found to be associated with incident CVEs. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT05146414.

Identification of a novel genetic locus associated with immune-mediated thrombotic thrombocytopenic purpura.

Immune thrombotic thrombocytopenic purpura (iTTP) is an ultra-rare, life-threatening disorder, mediated through severe ADAMTS13 deficiency causing multi-system micro-thrombi formation, and has specific human leukocyte antigen associations. We undertook a large genome-wide association study to investigate additional genetically distinct associations in iTTP. We compared two iTTP patient cohorts with controls, following standardized genome-wide quality control procedures for single-nucleotide polymorphisms and imputed HLA types. Associations were functionally investigated using expression quantitative trait loci (eQTL), and motif binding prediction software. Independent associations consistent with previous findings in iTTP were detected at the HLA locus and in addition a novel association was detected on chromosome 3 (rs9884090, P=5.22x10-10, odds ratio 0.40) in the UK discovery cohort. Meta-analysis, including the French replication cohort, strengthened the associations. The haploblock containing rs9884090 is associated with reduced protein O-glycosyltransferase 1 (POGLUT1) expression (eQTL P<0.05), and functional annotation suggested a potential causative variant (rs71767581). This work implicates POGLUT1 in iTTP pathophysiology and suggests altered post-translational modification of its targets may influence disease susceptibility.

Campylobacter infection in 4 patients treated with ibrutinib.

Ibrutinib is a Bruton tyrosine kinase (BTK) inhibitor used in B-cell lymphoproliferative disorders. Patients with genetic BTK deficiency are susceptible to recurrent and severe Campylobacter infections. We report 4 patients treated with ibrutinib who developed chronic or extra-digestive campylobacteriosis resembling ibrutinib-related adverse events including diarrhea (n = 4), panniculitis (n = 2), and arthritis (n = 1). Microbiological explorations identified Campylobacter jejuni (n = 3) or Campylobacter coli (n = 1). All the patients completely recovered after a short course of oral antibiotic therapy. In patients treated with ibrutinib presenting with chronic diarrhea, dermatological, or rheumatological manifestations, campylobacteriosis should be ruled out before attributing the symptoms to ibrutinib and discuss its discontinuation.

Metagenomic next-generation sequencing restores the diagnosis of a rare infectious complication of B cell depletion.

A 45-year-old female patient receiving rituximab for B cell non-Hodgkin follicular lymphoma presented unexplained recurrent fever, abdominal discomfort, and pollakiuria. We performed shotgun metagenomic sequencing from peri-kidney collection that identified a co-infection with Mycoplasma hominis and Ureaplasma urealyticum. The patient recovered with sequelae after appropriate antibiotic treatment was given.

Shiga Toxin-Associated Hemolytic Uremic Syndrome in Adults, France, 2009-2017.

We conducted a retrospective study on hemolytic uremic syndrome caused by Shiga toxin-producing Escherichia coli (STEC) in 96 adults enrolled in the cohort of the National Reference Center for Thrombotic Microangiopathies network in France during 2009-2017. Most infections were caused by STEC strains not belonging to the O157 or O104 serogroups. Thirty (31.3%) patients had multiple risk factors for thrombotic microangiopathy. In total, 61 (63.5%) patients required dialysis, 50 (52.1%) had a serious neurologic complication, 34 (35.4%) required mechanical ventilation, and 19 (19.8%) died during hospitalization. We used multivariate analysis to determine that the greatest risk factors for death were underlying immunodeficiency (hazard ratio 3.54) and severe neurologic events (hazard ratio 3.40). According to multivariate analysis and propensity score-matching, eculizumab treatment was not associated with survival. We found that underlying conditions, especially immunodeficiency, are strongly associated with decreased survival in adults who have hemolytic uremic syndrome caused by STEC.

Pure red cell aplasia in systemic lupus erythematosus, a nationwide retrospective cohort and review of the literature.

OBJECTIVES: To characterize the clinical and biological course, management and response to treatment in SLE-associated pure red cell aplasia (PRCA). METHODS: This was a nationwide, multicentre, retrospective cohort study. From 2006 to 2018, we included adults with a diagnosis of PRCA supported by bone marrow examination and SLE or biologic manifestations of SLE after ruling out parvovirus B19 infection. RESULTS: We enrolled 24 patients (20 women). SLE was diagnosed before PRCA for 14 patients (median delay 81 months). At PRCA diagnosis, mean age, haemoglobin level, and reticulocyte and differential erythroblast count were 39.2 (13.2) years, 62 ( 20) g/l, 9.1 (7.6) × 109/l and 2.8 ( 2.5)%, respectively. Eleven (45%) patients experienced multiple PRCA flares (median 6, range 2-11). CS therapy resulted in only three complete sustained responses, and 19 (79%) patients required immunosuppressive agents with highly variable regimens. After a median follow-up of 76 months (range 13-173), 17 (71%) patients showed complete response for PRCA, 5 (21%) partial response and 2 (8%) treatment failure. In total, 21 (87%) patients required red blood cell transfusion; 5 had a diagnosis of transfusion-related iron overload. Eighteen (75%) patients experienced severe infectious events requiring hospitalization. CONCLUSION: SLE-associated PRCA is a severe condition. Repeated red blood cell transfusions and several lines of immunosuppressant therapy are mostly required, with high risk of severe infectious events and iron overload. Despite sustained response for PRCA and SLE obtained in most patients, the best therapeutic strategy remains to be determined.

Highly sensitive serum cardiac troponin T and cardiovascular events in patients with systemic lupus erythematosus (TROPOPLUS study).

OBJECTIVE: Identification of biological markers able to better stratify cardiovascular risks in SLE patients is needed. We aimed to determine whether serum cardiac troponin T (cTnT) levels measured with a highly sensitive assay [high sensitivity cTnT (HS-cTnT)] may predict cardiovascular events (CVEs) in SLE. METHOD: All SLE patients included between 2007 and 2010 in the randomized, double-blind, placebo-controlled, multicentre PLUS trial were screened. Patients with no past history of CVE at inclusion and a follow-up period of >20 months were analysed. HS-cTnT concentration was measured using the electrochemiluminescence method on serum collected at PLUS inclusion. The primary outcome was the incident CVE. Factors associated with the primary outcome were identified and multivariate analysis was performed. RESULTS: Overall, 442 SLE patients (of the 573 included in the PLUS study) were analysed for the primary outcome with a median follow up of 110 (interquartile range: 99-120) months. Among them, 29 (6.6%) experienced at least one CVE that occurred at a median of 67 (interquartile range: 31-91) months after inclusion. Six out of 29 patients had more than one CVE. In the multivariate analysis, dyslipidaemia, age and HS-cTnT were associated with the occurrence of CVE. Kaplan-Meier analysis showed that a concentration of HS-cTnT > 4.27 ng/l at inclusion increased by 2.7 [hazard ratio 2.7 (95% CI: 1.3, 5.6), P =0.0083] the risk of CVE in SLE. CONCLUSION: HS-cTnT measured in serum is the first identified biomarker independently associated with incident CVE in SLE patients.

Kaposi sarcoma-associated herpesvirus/human herpesvirus 8-associated lymphoproliferative disorders.

Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 is associated with multicentric Castleman disease (MCD) and primary effusion lymphoma (PEL). In MCD, infected B cells, although polyclonal, express a monotypic immunoglobulin Mλ phenotype, probably through editing toward λ light chain in mature B cells. They are considered to originate from pre-germinal center (GC) naive B cells. Both viral and human interleukin-6 contribute to the plasmacytic differentiation of these cells, and viral replication can be observed in some infected cells. PEL cells are clonal B cells considered as GC/post-GC B cells. One can also hypothesize that they originate from the same infected naive B cells and that additional factors could be responsible for their peculiar phenotype.

Immune thrombotic thrombocytopenic purpura in older patients: prognosis and long-term survival.

Older age is associated with increased mortality in immune thrombotic thrombocytopenic purpura (iTTP). Yet, data are scarce regarding iTTP occurring among older patients. To assess clinical features and long-term impact of iTTP on mortality in older patients (>60 years old), characteristics and prognoses of adult iTTP patients enrolled in the French Reference Center for Thrombotic Microangiopathies registry between 2000 and 2016 were described according to age (<60 years old or ≥60 years old). Long-term mortality of iTTP older survivors was compared with that of non-iTTP geriatric subjects. Comparing, respectively, older iTTP patients (N = 71) with younger patients (N = 340), time from hospital admission to diagnosis was longer (P < .0001); at diagnosis, delirium (P = .034), behavior impairment (P = .045), renal involvement (P < .0001), and elevated troponin level (P = .025) were more important whereas cytopenias were less profound (platelet count, 22 × 103/mm3 [9-57] vs 13 × 103/mm3 [9-21], respectively [P = .002]; hemoglobin level, 9 g/dL [8-11] vs 8 g/dL [7-10], respectively [P = .0007]). Short- and mid-term mortalities were higher (P < .0001) and increased for every 10 years of age range. Age ≥60 years, cardiac involvement, increased plasma creatinine level, and total plasma exchange volume were independently associated with 1-month mortality. Compared with a non-iTTP geriatric population, older survivors showed an increased long-term mortality (hazard ratio = 3.44; P < .001). In conclusion, older iTTP patients have atypical neurological presentation delaying the diagnosis. Age negatively impacts short-term but also long-term mortality.