Low ANA Research Articles

#2991 Two cases of chronic lymphocytic leukemia associated immunotactoid glomerulopathy: variable clinical presentation, close hematological collaboration

Abstract Background and Aims Immunotactoid glomerulopathy (ITG) is a very rare disease, observable in less than 0.1% of native kidney biopsy samples. It is most often associated with hematological diseases. We confirmed ITG in two cases among our 850 kidney biopsy patients in the past 9 years. In both patients, chronic lymphocytic leukemia (CLL) was the underlying cause. Method Case 1, a 56-year-old man was admitted due to severely increased proteinuria (2 g/day) with preserved renal function, while case 2, a 57-year-old-man was referred with rapidly decreasing eGFR (20 ml/min/1.73m2) with nephrotic syndrome (serum albumin level was 24 g/l). In case 1, no previous history of hematological disease was known, in case 2, CLL - that did not require treatment - was diagnosed half a year before admission. He still had no kidney involvement even 3 months after the CLL diagnosis. We performed kidney biopsy. Light microscopy revealed mesangial proliferative-atypical membranous pattern in case 1, and membranoproliferative pattern in case 2. Immunofluorescence microscopy showed IgG1-lambda deposition, electron microscopy confirmed the organised deposits, microtubular structures with a diameter of 44 nanometers in both cases. Neither monoclonal gammopathy nor systemic immune disease was confirmed. In case 2, low titer ANA positivity, low C3 and high anti-C1q antibody titer was detected, lupus nephritis was ruled out. Previously, lymphocyte count was slightly increased in case 1, CLL was confirmed after kidney biopsy. The immunoglobulin heavy chain variable region gene somatic hypermutation status was borderline in case 1, while in the other case it was unmutated. Fluorescein in situ hybridisation revealed trisomy 12 in both cases. In case 1, chemotherapy was not used due to Rai stage 0, and with appropriate antihypertensive treatment, we could preserve kidney function, and proteinuria was persistently low (below 1 g/day). In case 2, due to Rai stage 1, and progressive renal and lymph node involvement, immunochemotherapy was started (obinutuzumab-venetoclax). Three months later eGFR stabilized at 27 ml/min/1.73 m2, proteinuria decreased below 1 g/day, the C3 level normalized. Conclusion ITG can develop in the early stages of CLL, but it can also indicate CLL progression. The light microscopy histological pattern and, in parallel, the clinical appearance can be of varying severity. Immunochemotherapy resulting reduction of CLL tumor burden and cessation of complement damage, both play a role of improving renal status. Our cases also draw attention to the need for close collaboration with hematologists.

CD19/BCMA CAR-T Cell Therapy for Refractory Systemic Lupus Erythematosus - Safety and Preliminary Efficacy Data from a Phase I Clinical Study

Background: Despite significant advances in the treatment of systemic lupus erythematosus (SLE), a subset of patients continue to experience severe progression of their disease despite multiple immunosuppressive and targeted therapies. Furthermore, to date, drug-free remission and seroconversion have been difficult to achieve in SLE. CD19 single-targeted chimeric antigen receptor (CAR) T-cell therapies have shown promising efficacy in SLE but have been unable to attack CD19-negative, long-lived plasma cells, which produce numerous antibodies.This trial aims to study the safety, tolerability and preliminary efficacy of deep B-cell clearance in patients with refractory SLE using autologous anti-CD19 and BCMA CAR-T cells. Method: The CAR product was manufactured by Shanghai YaKe Biotechnology Ltd. The clinical study was conducted in a dose-escalation format. T cells were enriched from patient's peripheral blood, transfected with lentiviral vectors and expanded. After lymphodepleting chemotherapy with cyclophosphamide/fludarabine (D-4 to D-2), patients receive a single infusion of 1-2x106 CD19 CAR-T cells and BCMA CAR-T cells per kilogram of body weight at D0. On the first day of chemotherapy initiation , all SLE-related immunosuppressants, biologics, etc. were discontinued except for a few patients who were maintained on low-dose prednisolone. Tolerability was assessed by monitoring cytokine release syndrome (CRS), immune-related effector cell neurotoxicity syndrome (ICANS), and infections. Initial efficacy was assessed by attainment of lupus low disease activity state (LLDAS), dsDNA antibody and ANA seroconversion, and discontinuation of all SLE-specific therapies. Results: As of July 31, 2023, 12 patients with refractory SLE were treated with CD19/BCMA CAR-T cells with a median follow-up of 118.5 (45-524) days. All patients had active severe SLE and had received glucocorticoids, hydroxychloroquine, tacrolimus, total glucosides of paeony, merti-macrolide, leflunomide, azathioprine, methotrexate, cyclophosphamide, immunoglobulin, rituximab, belimumab, and Tetracycline before treatment with CAR-T cells, which were standard treatments that were either ineffective or difficult to withdraw.3 patients received 1x10^6/kg of each of CD19 CAR-T cells and BCMA CAR-T cells, and 9 patients received 2x10^6/kg of each of CD19 CAR-T cells and BCMA CAR-T cells 2x10^6/kg. CAR-T cells were prepared successfully in all patients. BCMA CAR-T achieved expansion in all patients, while CD19 CAR-T did not expand in 1 patient, and expansion of CAR T cells preceded depletion of circulating B cells. All patients developed grade 1 CRS, which manifested as controllable fever, and no ICANS occurred. 11 patients (91.7%) developed grade 4 hematologic toxicity, and 1 patient (8.3%) developed grade 3 hematologic toxicity. Within 6 months of CAR-T treatment, 2 patients were infected with neocoronavirus, 1 patient developed gastrointestinal tract infection, and 1 patient developed pulmonary infection , and all of them recovered after treatment. The SLEDAI-2K score decreased in all patients, from a mean of 18.3 to 1.5. Low-level proteinuria persisted in some patients, possibly due to previously accumulated glomerular filtration impairment. All patients met LLDAS criteria and were able to successfully discontinue all SLE-related medications, including glucocorticoids. peripheral blood B cells recovered at approximately 3 months after CAR-T therapy. To date, no SLE flares have occurred. Conclusions: These data suggest that CD19/BCMA CAR-T cell therapy is well tolerated and can induce rapid and durable remission in severe refractory SLE.

#2627 IGA-DOMINANT POSTINFECTIOUS GLOMERULONEPHRITIS, “THE OTHER SIDE OF THE COIN”: A CASE REPORT

Abstract Background and Aims Postinfectious glomerulonephritis (PIGN) is a disease presented as nephritic syndrome with hypocomplementemia usually secondary to a skin or throat infection by beta hemolytic Streptococcus and with histopathological findings of endocapillary proliferation, C3 deposits along the capillary wall and mesangium, subepithelial immune complex deposits and IF positive for IgG. There are other unusual presentations of PIGN with IgA dominance or C3-IgA codominance. Method A 58-year-old Guatemalan male, with history of one-week duration pain in the right upper quadrant associated with jaundice, diagnosed with cholangitis and intravenous antibiotics use. History of consumption of 10 beers a month for 40 years. No other medical history. During hospitalization, presented a lower-limb cellulitis, for which clindamycin was started. Blood cultures were taken and were positive for S. epidermidis and AKI (Cr 2.84 mg/dl) was observed, associated with de novo appearance of hematuria (80% acanthocytes), proteinuria (580mg/day) and hypertension. Diagnostic approach for nephritic syndrome was performed obtaining: C3 0.592 (low) ANA, ANCAs, HIV-HCV-HBV negative, total cholesterol 184 mg/dl, albumin 2.78 g/dl. Results Renal biopsy was performed and reported: PIGN with IgA dominance with extra capillary proliferation. Reason why pulses of methylprednisolone were given for 3 days and then oral prednisone (1 mg/kg/day), progressively decreasing it until it was discontinued. Resolved the soft tissue infection and was discharged. At 1-month follow-up as outpatient, was evidence of a 50% decrease in proteinuria compared to baseline, disappearance of hematuria but with persistent of high Cr (2.09 mg/dl). Conclusion IgA-dominant PIGN is characterized by usually presenting in patients >60 years with DM, alcohol consumption and staphylococcal skin infections. It can present hypocomplementemia and histopathological findings are characterized by IgA dominance over C3 and no IgG in IF. Elevated serum IgA levels may be involved in the pathogenesis. Treatment is based on eradication of the infection with antibiotics and in some cases the use of steroids is suggested depending on the aggressiveness of the lesion and the presence of crescents in the renal biopsy. It has worse prognosis than the traditional PIGN.

Myositis autoantibodies detected by line blot immunoassay: clinical associations and correlation with antibody signal intensity.

The aim of this study is to assess the relationship between myositis specific (MSA) and myositis associated (MAA) antibodies and diagnosis (including idiopathic inflammatory myopathies [IIM] and other systemic autoimmune diseases [SAID]), and to explore the impact of antibody signal intensity in diagnostic accuracy. We retrospectively reviewed all the serum samples obtained from patients tested for MSA/MAA by line immunoassay (LIA) between 01/01/2018 and 31/12/2020 in Ramón y Cajal University Hospital (Spain). Clinical true positive (CTP) MSAs and MAAs were defined as those patients with IIM or SAID with phenotypes expected of that MSA/MAA. Patients who did not have a phenotype compatible with that antibody were classified as clinical false positive (CFP). One hundred and thirty positive samples were analysed. Forty-six patients (33.38%) were classified as IIM, forty-two (32.3%) as SAID and forty-two (32.3%) as non-IIM/SAID. Among these 130 patients, 164 MSA/MAA were detected. Eighty-five (51.8%) positive MSA/MAA were classified as CTP, and seventy-nine (48.2%) as CFP. Strongly positive antibodies were more frequently CTP (35/47, 74.5%) than weak positives (54/68, 36.8%), (p ˂ 0.001). Antibodies classified as CTP had a higher signal intensity than CFP (36.77 AU vs 20.00 AU, CI95% 7.79-22.09, p ˂ 0.001). The probability of a CFP was associated to negative ANA, low ANA titer, and multiple positive MSA/MAA (p˂ 0.001). In this study, we confirmed that CFP results using LIA are frequent, and are associated with low signal intensity MSA/MAA, negative ANA, lower titer ANA, and with multiple positive samples.

FATAL CASE OF FULMINANT HEPATIC FAILURE DUE TO HERPES SIMPLEX VIRUS REACTIVATION IN SETTING OF IMMUNOSUPPRESSION FROM CHRONIC STEROID AND METHOTREXATE USE: A RARE PRESENTATION

FATAL CASE OF FULMINANT HEPATIC FAILURE DUE TO HERPES SIMPLEX VIRUS REACTIVATION IN SETTING OF IMMUNOSUPPRESSION FROM CHRONIC STEROID AND METHOTREXATE USE: A RARE PRESENTATION

Interpreting Rheumatology Laboratory Tests

Interpreting Rheumatology Laboratory Tests

O08 A case of juvenile systemic lupus erythematosus with pyrexia of unknown origin

Case report - IntroductionAn 18-year-old young man with diagnosis of Juvenile SLE with lupus nephritis maintained in remission on Mycophenolate Mofetil (MMF), presented with high-grade fever without focus close to his 18th birthday. History or examination did not point to any focus of infection, but blood tests showed systemic inflammation. Extensive investigations, including extended infection screen and bone marrow aspiration, were negative. His blood tests were suggestive of macrophage activation syndrome with no clinical or laboratory evidence of flare of lupus. MRI scan revealed extensive para-aortic lymphadenopathy and a diagnosis of classical Hodgkin's lymphoma confirmed on lymph node biopsy.Case report - Case descriptionInterestingly he first presented with fever and cervical lymphadenopathy at 13 years of age to local hospital, when a biopsy had revealed lymphoma but the diagnosis was changed to SLE following review at tertiary hospital. He was started on steroids and low-dose methotrexate. He later developed facial swelling, abdominal distension and groin swelling, following which he was referred to tertiary renal centre. His examination revealed scarring malar rash, anaemia, ankle and scrotal oedema, ascites and pleural effusion. His investigations showed anaemia, thrombocytopaenia, ESR over 100mm/hour, hypoalbuminaemia, low complement levels, positive ANA and double-stranded DNA. He had nephrotic range proteinuria and renal biopsy showed Class V lupus nephritis. He was treated with intravenous and later weaning dose of oral steroids and started on MMF. He remained in remission on a stable dose of MMF, except for brief flare of proteinuria, which settled with short course of oral steroids.A few months before his eighteenth birthday, he presented to local hospital with recurrent episodes of high-grade fever with no clear focus. He was twice managed with broad spectrum antibiotics, despite negative septic screen and an extended infection screen including viral PCRs and IGRA for tuberculosis. He had no focal symptoms or symptoms to suggest flare of underlying lupus, but had loss of appetite and loss of weight. He developed splenomegaly with increasing inflammatory markers and fall in all cell lines of full blood count with deranged coagulation. He satisfied the clinical and laboratory criteria of the preliminary Diagnostic Guidelines for Macrophage Activation Syndrome in JSLE (2009), following which he was commenced on three days of IV methylprednisolone following normal bone marrow aspirate. However, fever recurred after initial response and MRI scan revealed mediastinal and para-aortic lymphadenopathy, and a diagnosis of classical Hodgkin's lymphoma was confirmed on lymph node biopsy.Case report - DiscussionThis young man initially presented with fever and cervical lymphadenopathy, when a diagnosis of lymphoma was made. Yet, following review of the biopsy at the local tertiary centre and the abnormal immunological profile, a diagnosis of lupus was made. He then developed nephrotic syndrome, when a diagnosis of lupus nephritis was confirmed on biopsy. Other clinical and laboratory profile (raised ESR, hypocomplementeamia, serositis and haematological parameters) corroborated the diagnosis. He responded well to steroids and immunosuppression, when he presented with fever again. He had no evidence of flare of underlying lupus or any infection, but blood tests and splenomegaly pointed to macrophage activation syndrome (MAS). A negative bone marrow examination suggested that pancytopaenia was unlikely to be due to bone marrow infiltration, which is why he was treated with steroids. Yet, when fever recurred, MRI was arranged to investigate further, which eventually led to revelation of lymphadenopathy and biopsy, which eventually led to the right diagnosis. Another dilemma was if his MAS was to respond to steroids, whether we should change his baseline immunosuppression which had worked well so far for him and if we chose to, what would be the best agent.Case report - Key learning points1. Although extremely uncommon, children and young people with rheumatic diseases can develop malignancy, which may be unrelated to the primary condition or the therapeutic agents used. Unexplained symptoms in the absence of flare of underlying condition and with infections ruled out, warrant extension of investigations to rule out an underlying malignancy.2. Diagnosis of secondary MAS in a rheumatological condition without any evidence of flare of the underlying condition should be viewed as suspicious and warrants more investigations to rule out other causes.3. In patients who develop MAS, there are very few agents which work for both lupus and MAS, choosing an agent which treats both conditions is challenging.

Pediatric systemic lupus erythematosus with lupus anticoagulant hypoprothrombinemia syndrome—A case series with review of literature

Lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) is a rare phenomenon that leads to concomitant thrombosis and hemorrhage in children with SLE. LAHPS in pediatric SLE (pSLE) has a protracted course requiring long-term immunosuppressive therapy. Due to the rarity of this syndrome and paucity of reported cases, there is lack of standardized management. We herewith report 5 children with pSLE with LAHPS.Methodology: We retrospectively reviewed clinical features, laboratory features, treatment and outcome for 5 children with lupus anticoagulant hypoprothrombinemia syndrome with SLE and a review of literature of similar cases published. Mean age of presentation was 10.2 ± 2.38 years (mean ± SD) and female to male ratio was 4:1. All children presented with mild to severe bleeding manifestations like gum bleed, epistaxis, hematuria, menorrhagia and subarachnoid bleed. Coagulation profile revealed prolonged PT and aPTT, with low prothrombin levels and positive Lupus anticoagulant in all children. Mixing studies were characteristic in these children. On comparing laboratory parameters majority had low C3, C4 levels, ANA and anti-DsDNA antibody positivity and three children had anticardiolipin positivity. One child had lupus nephritis along with LAHPS at presentation. All responded well to steroids and supportive measures. High index of suspicion is needed when child with lupus presents with bleeding manifestations for early diagnosis and treatment.

Clinical characteristics and poor predictors of anti-NXP2 antibody-associated Chinese JDM children

BackgroundJuvenile dermatomyositis (JDM) is a rare and sometimes fatal disease in children. The anti-NXP2 antibody is one of the most common antibodies and muscle ischaemia associated with NXP2 autoantibodies was a severe subtype of JDM. Further information is needed regarding clinical characteristics and factors associated with poor prognosis. But there are no reports about clinical characteristics and high risk factor of poor prognosis. For the first time, we introduced the clinical characteristics and poor predictors of anti-NXP2 antibody-associated juvenile dermatomyositis in Chinese children.MethodsTwenty-six patients with anti-NXP2 antibody-related JDM from 85 JDM Chinese patients were diagnosed from January 2016 to November 2019. Logistic regression was used to analyze the risk factors for refractory cases and mortality.ResultsThe ratio of male to female was 1:1.9. The median age of onset was 4.5 (1–13) years. Twenty-four cases (92.3%) had rash and muscle weakness. Treatments included glucocorticoids, immunosuppressive agents, biological agents (7 cases), plasma exchange, Janus kinase inhibitor (7 cases) and autologous stem cell transplant (1 case). Refractory JDM patients (11/26, 42.3%) were associated with edema, skin ulcer, muscle strength<=grade 3, CD4/CD8 ratio < 1.4 and ferritin > 200μg/ml. Among 6 cases (6/26, 23.1%) with severe gastrointestinal involvement, 5 cases died and 1 case survived after autologous stem cell transplant (ASCT). The risk factors for gastrointestinal involvement and mortality were edema, skin ulcer, severe muscle weakness (dysphagia/ hoarseness/ soft voice), BMI < 15 and ANA positive.ConclusionsEdema, skin ulcer and severe muscle weakness predicted refractory disease, GI involvement, and mortality in anti-NXP2 antibody-positive JDM of Chinese children. Decreased CD4/CD8 ratio and high ferritin related with refractory cases, and very low BMI and ANA (+) are probably, associated with gastrointestinal involvement and mortality.Trial registrationhttp://www.chictr.org.cn/showproj.aspx?proj=49846.

A Fatal Case of Systemic Lupus Erythematosus Complicated with Diffuse Alveolar Hemorrhage

Introduction: SLE is a multisystem autoimmune disease with variable clinical presentation. DAH is a rare but catastrophic manifestation of SLE with high mortality, requiring early, intensive therapy. Case Presentation: A 31-year-old female presented with low-grade fever and joint pains for six weeks associated with alopecia, anorexia, and weight loss. She had pale and had cervical lymphadenopathy, moderate hepatomegaly, and splenomegaly. Hb level was 9.2mg/dL, with a platelet count of 144 × 103/µL. The ESR was 65mm/hour, and the CRP level was 36 mg/L with a UPCR of 332mg/g. She had low C3, C4 levels, positive ANA, and dsDNA titer. A renal biopsy revealed class 3 lupus nephritis. Twenty days after, she was readmitted with acute onset of pleuritic chest pain, cough, and dyspnea, where she was hemodynamically unstable with SpO₂ of 85% on air. The Hb level was 8.6 g/dL with a platelet count of 106 × 103/µL. Her condition deteriorated despite standard medical care, where the Hb level and SpO₂ dropped to 5.6 d/dL and 65%, respectively, even after blood transfusions, intubation, and artificial ventilation. The chest X-ray revealed bilateral large whitish hazy shadows, and the HRCT scan revealed diffuse bilateral pulmonary hemorrhages. Then she was transferred to the ICU, and there she was started with broad-spectrum antibiotics, methylprednisolone, and plasmapheresis. However, after one week of ICU stay, her renal functions worsened, and she was initiated on CRRT. However, despite all the resuscitation efforts, she succumbed following a cardiac arrest. Conclusion: DAH is a rare catastrophic complication of SLE, which usually presents in patients with an established diagnosis of SLE, even on medical therapy. The diagnosis of DAH is problematic because it mimics a severe pulmonary infection. Early detection and aggressive management are warranted to improve affected patients' outcomes and quality of life.

S2881 Lupus Enteritis as the Unique Manifestation of Lupus Flare - Report of 2 Cases

INTRODUCTION: Gastrointestinal (GI) symptoms are common in patients with systemic lupus erythematous (SLE) but real GI involvement is rare. Lupus enteritis refers to either vasculitis or inflammation of the bowel wall. It is present in 0.2–5.8% of patients usually in the context of high-SLE activity. The symptoms are nonspecific and can be life-threatening especially if the treatment is delayed. We present two cases of lupus enteritis as the sole manifestation of SLE flare. CASE DESCRIPTION/METHODS: Case 1. 19-year-old female with no prior SLE diagnosis was admitted with four months of persistent diarrhea, vomiting, and epigastric pain. Workup revealed Mg 0.5 mg/dl, K 2.5 mEq/l, Hb 11.2 g/dl, CRP 1.40 mg/dl, and subnephrotic proteinuria. Infectious workup was negative. CT scan showed diffuse thickening and enhancement of the small and large bowel wall. Upper and lower endoscopy with biopsy revealed nonspecific edema and chronic inflammation. Further evaluation showed low complement levels, positive ANA ( > 1:160), anti-dsDNA ( > 300 IU/ml), SSA, SSB, anti-histone Ab, and lupus anticoagulant. IV methylprednisolone was started with marked improvement, later transitioned to hydroxychloroquine, azathioprine, and prednisone with taper dose. Case 2. 49-year-old female, SLE diagnosed in 2017, no treatment for 2 years was admitted with one month of persistent vomiting and abdominal pain. Evaluated initially with upper and lower endoscopy which revealed Barret’s esophagus. Workup revealed Na 132 mEq/L, Mg 1.6 mg/dl, lymphopenia (200 k/uL), elevated CRP (0.67 mg/dl), and subnephrotic proteinuria. Negative infectious workup. Further evaluation showed ANA ( > 1:160), Anti Smith ( > 8), anti-dsDNA (4 IU/ml), SSA ( > 8), and low complement levels. CT scan with diffuse thickening and enhancement of the small bowel and entire colon and rectum. IV methylprednisolone and a short course of IV erythromycin was started with significant improvement; later transitioned to hydroxychloroquine, azathioprine, and prednisone with taper dose. Both patients did not present recurrence of symptoms during the next 3 months. DISCUSSION: Lupus enteritis is very rare as an unique feature of SLE flare. Current knowledge is scarce. CT scan is the test of choice. It usually responds to steroids. Steroid-sparing agents are required in severe-relapsing cases. Our cases highlight the difficult diagnosis of this disease. Identifying this condition is crucial to avoid complications as bowel necrosis or perforation.Figure 1.: Contrast enhanced abdomen CT scan coronal axial views revealed “target” sign that represent circumferential thickening of the intestine wall. In this case affecting both small and large intestine.Figure 2.: Contrast enhanced abdomen CT scan showing diffuse thickening of the small and large intestine wall. "Target" sign can also be appreciated here.

He Shou Wu (Polygonum multiflorum)-Induced Hepatocellular Hepatitis

He Shou Wu (Polygonum multiflorum)-Induced Hepatocellular Hepatitis

Atypical Plasmacytic Proliferation in a Case of C3 Glomerulopathy: Pathophysiology Demystified.

An 11-year-old Hispanic female underwent evaluation of asymptomatic proteinuria and hematuria. The patient denied fever, edema, and gross hematuria. Urinalysis showed mild proteinuria, and a urine microscopic examination revealed red blood cells. Screening tests for glomerulonephritis revealed a low C3 and negative ANA, ASO, DNAse-B, and ANCA. Histological examination of a renal biopsy specimen showed glomeruli with endocapillary proliferation, a predominant C3 deposition in the capillary loops by immunofluorescence, and electron dense deposits in the mesangium, paramesangium, and capillary walls by electron microscopy consistent with a diagnosis of C3 glomerulopathy. An interstitial plasmacytosis was also present with focal clustering of plasma cells, which were found to be kappa light chain restricted by in situ hybridization suggestive of a clonal proliferation. One can speculate that these plasma cells may be directly responsible for the renal pathology that was seen.

Effects of N-Arachidonoylethanolamine on the quality of platelets stored in M-sol platelet preservative solution in vitro

This study was purposed to investigate the effects of N-Arachidonoylethanolamine (ANA) on the quality of platelets (Plt) stored in Plt M-sol preservative solution at 22 ± 2°C. Samples taken from collecting apheresis Plt by the Amicus instrument and splited into two equal parts were stored in Plt M-sol preservative solution on a shaker at 22 ± 2°C. Different working concentrations of ANA (from 0.1 to 50 µmol/L) were then added into one part of stored Plt as the experimental group, the other without ANA was used as the control group. The viability of Plts stored at 22 ± 2°C for 7 days was evaluated by MTT colorimetric assay. The most effective concentration of ANA was selected and added to the subsequent experimental group. Plt count (BPC), mean Plt volume (MPV), Plt distribution width (PDW), phosphatidyl serine (PS) and soluble P-selectin were detected on the 1(st), 5(th), 7(th), 9(th) and 11(th) day of storage. The results showed that the most effective working concentration of ANA was 0.5 µmol/L, which showed significant increasing Plt viability (91.23 ± 5.44%) compared to the control group (62.54 ± 4.79%). Thus, ANA concentration at 0.5 µmol/L was choose to perform subsequent experiments. During 11 days of storage, the BPC, MPV and PDW were not changed significantly between the experimental group and control group, although there was decreasing trend in the BPC and increasing trends in MPV and PDW in the two groups. The rate of Plt PS positive was enhanced during the storage period: the rate of PS positive in experimental group increased from 7.69 ± 1.82% to 10.74 ± 1.78% while it in control group increased from 11.21 ± 2.03% to 15.37 ± 1.95%, with significant differences between the two groups (P < 0.05) on the 9(th) and 11(th) day of storage, respectively. Soluble P-selectin contents in experimental group on the 9(th) and 11(th) day of storage were 30.19 ± 2.03 ng/ml and 34.52 ± 2.64 ng/mL, respectively, while those in control group were 39.18 ± 2.66 ng/ml and 43.23 ± 2.58 ng/ml, respectively, with significant differences between the two groups (P < 0.05). It is concluded that the extended storage of Plt in M-sol treated with low concentration ANA can potentially alleviate Plt storage lesions.

AB0769 Clinical, laboratory, neuroimaging and treatment of primary versus secondary central nervous system vasculitis

BackgroundPrimary central nervous system vasculitis (PCNSV) is an uncommon condition in which vascular inflammatory lesions are limited to the brain and spinal cord. Diagnostic criteria include a newly acquired neurological...

Hypocomplementaemic immune complex tubulointerstitial nephritis

We report a rare cause of rapidly progressive renal failure associated with low complement, positive ANA but negative anti DS-DNA. A renal biopsy demonstrated tubulointerstitial nephritis with positive immunoglobulin staining involving the interstitium and tubular basement membrane but glomerular sparing. A review of the literature and differential diagnosis are discussed.

Systemic Lupus Erythematosus After Renal Transplantation: Is Complement a Good Marker for Graft Survival?

Background Renal transplantation is considered a safe procedure for patients with systemic lupus erythematosus (SLE). However, the recurrence of disease and its impact on graft survival remains controversial. Methods To analyze the presence of lupus serology activity during dialysis and its impact on lupus recurrence after transplantation, we performed a retrospective analysis of 23 lupus patients who received 26 kidney transplantations. Results Twenty-three patients received 26 renal transplantations from 1984 to 2003. Twelve patients presented pretransplant lupus activity (low complement and ANA > 1/40), without correlation with length of dialysis, but associated with proliferative glomerulonephritis (class IV) pretransplant. Among 26 grafts, 6 were lost in the first 6 months posttransplant. Among the remaining 20 functioning grafts, low complement activity occurred in 8, being associated with recurrence of immune deposits in 3 cases. Analysis of lupus activity showed that only one patient with a normal complement level posttransplant presented SLEDAI > 4, associated with persistent proteinuria and a graft biopsy without immune deposits. Graft survival was reduced in the presence of low complement posttransplantation. Conclusion Low complement levels after renal transplantation, in association with proteinuria may be considered to be a risk factor for recurrence of immune deposits, with a negative impact on graft survival.

Autoantibodies and self-reported health complaints in relatives of systemic lupus erythematosus patients: a community based approach

First-degree relatives (FDRs) and spouses to a population-derived cohort of lupus patients were investigated for the occurrence of selected autoantibodies and self-reported health complaints. A healthy reference population was included. The lupus population consisted of 103 index cases. A total of 275/375 available relatives accepted to enter the study. Two hundred and twenty-six/315 (72%) were FDRs and 49/60 (82%) were spouses. Serum was analysed for ANA using indirect immunofluorescence on Hep-2 cells at the following dilutions: 1:40, 1:80 and 1:160 and in addition sera were tested for anti-dsDNA, IgM RF, ACA (IgM, IgG), anti-beta2GPI (IgM, IgG) and antibodies to prothrombin. ANA positivity occurred more frequently in FDRs compared with spouses and controls at serum dilution 1:160 (10 versus 0% and 2.5%, respectively, P = 0.04 and P < 0.01), 1:80 (24 versus 4% and 5%, respectively, P = 0.003 and P < 0.001) and 1:40 (31 versus 10% and 10%, respectively, P = 0.006 and P < 0.0001). ANA positivity in FDRs occurred randomly, irrespective of family relationship. Fifty-three/184 versus 2/32 FDRs to patients with definite SLE (D-SLE) and incomplete SLE (I-SLE), respectively, tested ANA positive at 1:80 (P < 0.05). FDRs with ANA titer at 80 were affiliated to lupus probands with high SLICC scores (P < 0.05). Self-reported health complaints, cardiovascular/thromboembolic events in particular, were more frequent among FDRs than in spouses. The population-based approach adopted in the present study supports previous clinic-based evidence of an increased propensity for autoantibody occurrence in relatives to SLE patients. In FDRs, present ANA positivity was associated with increased prevalence of health complaints and ANA positivity in FDRs was related to the criterial burden and cumulated damage in corresponding lupus probands. The low ANA frequency among spouses of SLE patients argues against a significant autoantibody triggering effect of shared environment in adult life.

Pseudoxanthoma Elasticum Masquerading as Sjögren’s Syndrome

Pseudoxanthoma elasticum is an inherited disorder of abnormal calcification of elastic fibers in the skin, retina, and cardiovascular system. Herein, we report a patient who had dry eyes and mouth, keratoconjunctivitis sicca, and a low titer ANA at presentation. A lip biopsy was performed to confirm a clinical suspicion of Sjögren's syndrome; however, the histologic findings were diagnostic of pseudoxanthoma elasticum. Antibodies to Ro and La were negative. Subsequently, she was found to have skin and eye findings consistent with pseudoxanthoma elasticum. Although a causal relationship between keratoconjunctivitis sicca and pseudoxanthoma elasticum is not proven, salivary gland involvement with pseudoxanthoma elasticum may explain this patient's symptoms. Physicians should consider the diagnosis of pseudoxanthoma elasticum in patients who present with sicca symptoms without obvious cause, especially if cutaneous or ophthalmologic abnormalities, or both, are present. Careful monitoring for associated problems is needed as soon as pseudoxanthoma elasticum is diagnosed.

The Dysautonomia of Fibromyalgia May Simulate Lupus

Some overlap between features of fibromyalgia and systemic lupus erythematous (SLE) is well-recognized. Our objective is to describe eight patients with an original diagnosis of SLE, in whom, after re-evaluation, the multi-system symptoms could be explained on the basis of the dysautonomia that occurs in fibromyalgia.Seven of the eight patients were females. Their mean age was 31 years. All of them fulfilled the American College of Rheumatology criteria for fibromyalgia. Their lupus-like features that could later be explained by dysautonomia were the following: diffuse arthralgias with subjective feeling of swelling, malar erythema, syncopal episodes, profound fatigue, and distal vasospastic changes. Six patients had low titer ANA. None of the patients had signs of organic damage. Autonomic dysfunction was demonstrated by means of circadian studies of heart rate variability (6 patients) and/or tilt table testing (3 patients). We conclude that autonomic dysfunction may be an explanation for the lupus-like symptoms present in some patients with FM.