Anti-native DNA Research Articles

Autoimmune myelofibrosis revealing a systemic lupus erythematosus

Background: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease, characterised by multi-organ affections. Haematological involvement is a common manifestation of SLE, consisting of autoimmune peripheral cytopenia. Autoimmune myelofibrosis (AIMF) is a rare cause of cytopenia in SLE; it could precede or be concurrent with the diagnosis of SLE. There are few studies that describe this association. Case description: We report a case of AIMF revealing the diagnosis of SLE in a 34-year-old female, presented with episodes of gingival bleeding associated with peripheral inflammatory polyarthralgia, photosensitivity and deterioration of general condition. Clinical examination revealed a soft pitting oedema in the lower limbs. Laboratory investigations showed a pancytopenia, inflammatory biological syndrome, with positive 24-hour proteinuria and anti-native DNA antibodies. A bone marrow biopsy showed diffuse myelofibrosis associated with maturation disorders and no tumour infiltrate. Renal biopsy revealed proliferative glomerulonephritis class III with immune deposits. Conclusion: The association of AIMF with SLE has been rarely reported, and it could be another cause for cytopenia in SLE.

Clinical and Biological Lupus Induced by Infliximab in Crohn's Disease

The use of anti-TNFs in Crohn's disease (CD) is often associated with the appearance of antinuclear antibodies, and more rarely with anti-native DNA antibodies. Anti-TNF-induced lupus remains exceptional. We report the case of a 52-year-old woman, followed for colonic Crohn's disease, treated with Infliximab. After 12 months of treatment with anti-TNF alpha (Infliximab), the patient developed clinical and biological lupus with positive antinuclear antibodies (ANA) and anti-native DNA antibodies (IgG). Infliximab treatment was discontinued. Six months after stopping the treatment, the patient had no recurrence of clinical signs, and immunological examinations showed a marked decrease in total ANA and anti-native DNA antibodies (IgG).

Systemic Lupus Erythematosus: Female Versus Male

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease, uncommon in men. The study of gender differences in SLE has been the subject of several publications. The main aim of our study is to identify gender differences in terms of clinical manifestations, immunological profile, activity score, and disease evolution in our Moroccan population. Results: We analyzed 279 patients (21 men versus 258 women), with a mean age at diagnosis of 37.54 +/- 23.39 years for women and 42.74 +/- 16.33 years for men. A comparison of clinical and immunological manifestations showed that male patients had a higher prevalence of renal involvement, lymphopenia, leukopenia, and general signs, but the difference was not significant. However, we did establish a significant correlation between male sex and cardiac involvement (P=0.013) as well as neuropsychiatric involvement (P=0.05). We also observed a significant association with anti-SSA antibodies (p=0.007). Dermatological and articular events were more frequent in women than in men, with a statistically significant association between female gender and photosensitivity (p=0.037). There was also a statistically significant correlation between women with RNP antibodies (p = 0.016) and anti-native DNA antibodies (p=0.047). The outcome was good in 67% of men (vs. 86.2% p=0.802), with response to treatment and control of the disease, and poor in 33% of men (vs. 13.9% %, p=0.019). Conclusions: Our study reveals the influence of gender on certain clinical manifestations of SLE. Dermatological and articular manifestations are more frequent in women, whereas men present a more severe disease, with a higher frequency of renal, cardiac, and neurological involvement.

E53 Anti-OJ synthetase syndrome: a pediatric case report

Abstract Introduction The antisynthetase syndrome (ASS) is a connectivity with variable clinical expression. It is defined by the presence of anti-tRNA synthetase autoantibodies, associated with a clinical phenotype. It is an overlapping myositis associated with the presence of idiopathic inflammatory myopathy autoantibodies. Observation We report the case of an 11-year-old girl with no particular family history. The patient was diagnosed and treated as rheumatic fever 3 years ago and put on extencillin due to arthralgias of large right knee and hip joints with positive antistreptolysin O antibodies and history of repeated angina but without clinical improvement. The polyarthralgias progressed and became bilateral predominantly in the scapular and pelvic girdles associated with intense myalgias of three days before his admission leading to a motor deficit. A biological assessment was requested: creatine phosphokinase (CPK) = 1880UI/l; ASAT = 58UI/l; procalcitonin = 0.15; erythrocytesedimentation rate (ESR) was elevated. The immunological workup showed antibodies specific for myositis; antiRNA synthetase type OJ Positive. Results of immunological tests for other associated autoimmune diseases were (rheumatoid factor, anti-CyclicCitrullinated Peptide antibodies, anti SM and anti-Native DNA) negative. Electromyography showed no abnormalities. A muscle biopsy was not done. Chest CT scan showed no abnormalities. The patient was commenced on corticosteroid therapy at a dose of 1 mg/kg/day for 4–6 weeks then progressive weaning. Conclusion ASS is a complex and heterogeneous autoimmune connective disease. In the presence of extra-pulmonary signs and the positivity of the anti-tRNA synthetase antibody, the diagnosis is confirmed. The management often requires multidisciplinary approach.

Peripheral neuropathies during systemic diseases: Part I (connective tissue diseases and granulomatosis)

Systemic diseases (connective disease, granulomatosis) may be associated with peripheral neuropathies. The diagnosis can be complex when the neuropathy is the presenting manifestation of the disease, requiring close collaboration between neurologists and internists. Conversely, when the systemic disease is already known, the main question remaining is its imputability in the neuropathy. Regardless of the situation, the positive diagnosis of neuropathy is based on a systematic and rigorous electro-clinical investigation, specifying the topography, the evolution and the mechanism of the nerve damage. Certain imaging examinations, such as nerve and/or plexus MRI, or other more invasive examinations (skin biopsy, neuromuscular biopsy) enable to specify the topography and the mechanism of the injury. The imputability of the neuropathy in the course of a known systemic disease is based mainly on its electro-clinical pattern, on which the alternatives diagnoses depend. In the case of an inaugural neuropathy, a set of arguments orients the diagnosis, including the underlying terrain (young subject), possible associated systemic manifestations (inflammatory arthralgias, polyadenopathy), results of first-line laboratory tests (lymphopenia, hyper-gammaglobulinemia, hypocomplementemia), autoantibodies (antinuclear, anti-native DNA, anti-SSA/B) and sometimes invasive examinations (neuromuscular biopsy).

Sex-dependent Lupus Blautia (Ruminococcus) gnavus strain induction of zonulin-mediated intestinal permeability and autoimmunity.

Imbalances in the gut microbiome are suspected contributors to the pathogenesis of Systemic Lupus Erythematosus, and our studies and others have documented that patients with active Lupus nephritis have expansions of the obligate anaerobe, Blautia (Ruminococcus) gnavus (RG). To investigate whether the RG strains in Lupus patients have in vivo pathogenic properties in a gnotobiotic system, we colonized C57BL/6 mice with individual RG strains from healthy adults or those from Lupus patients. These strains were similar in their capacity for murine intestinal colonization of antibiotic-preconditioned specific-pathogen-free, as well as of germ-free adults and of their neonatally colonized litters. Lupus-derived RG strains induced high levels of intestinal permeability that was significantly greater in female than male mice, whereas the RG species-type strain (ATCC29149/VPI C7-1) from a healthy donor had little or no effects. These Lupus RG strain-induced functional alterations were associated with RG translocation to mesenteric lymph nodes, and raised serum levels of zonulin, a regulator of tight junction formation between cells that form the gut barrier. Notably, the level of Lupus RG-induced intestinal permeability was significantly correlated with serum IgG anti RG cell-wall lipoglycan antibodies, and with anti-native DNA autoantibodies that are a biomarker for SLE. Strikingly, gut permeability was completely reversed by oral treatment with larazotide acetate, an octapeptide that is a specific molecular antagonist of zonulin. Taken together, these studies document a pathway by which RG strains from Lupus patients contribute to a leaky gut and features of autoimmunity implicated in the pathogenesis of flares of clinical Lupus disease.

Left ventricular non-compaction in a juvenile systemic lupus erythematosus girl with Hashimoto’s thyroiditis: Case report and review of the literature

BackgroundLeft ventricular noncompaction (LVNC) is a structural abnormality of the left ventricular myocardium of unknown cause. Cardiovascular system involvement is an important manifestation in juvenile systemic lupus erythematosus (jSLE) and is a leading cause of morbidity and mortality. Aim of the workTo present a case of jSLE with LVNC and Hashimoto's thyroiditis. Case presentationA 15-year-old Tunisian girl with a history of Hashimoto's thyroiditis presented with paroxysmal chest pain, exertional dyspnea, headache, and polyarthralgia and was diagnosed with jSLE. Clinical examination revealed a febrile patient (39 °C). There was no tachypnea, no evidence of right heart failure, no audible murmurs on cardiac auscultation, and no edema of the lower limbs. Laboratory investigations revealed leucopenia (3500/mm3), anemia (10 g/dl), elevated erythrocyte sedimentation rate (ESR)(50 mm\\1sth), C-reactive protein (20 mg/l). Infections were excluded with multiple negative blood cultures and negative anti-streptolysin O antibodies. The antinuclear antibody (ANA) was positive homogenous at 1/10,000 and both anti-native DNA and anti-SSA were positive. The electrocardiogram (ECG) showed sinus tachycardia, the transthoracic echocardiography revealed pericarditis associated with a non-compacted LV and a small pericardial effusion. Thus, a cardiac magnetic resonance imaging (CMRI) was performed confirming LVNC with a hypertrabeculated sub-endocardium. There was no proteinuria, hypocomplementemia or cerebral vasculitis on cerebral magnetic resonance imaging (MRI). The patient received high-dose corticosteroids associated with beta-blocker therapy with a favorable outcome. ConclusionA rare case of LVNC which was accidentally discovered in a patient with jSLE and Hashimoto's thyroiditis is documented. Follow-up is needed for the development possible complications.

Case Report: Systemic lupus erythematous associated with thrombotic thrombocytopenic purpura, a diagnostic challenge

Thrombotic thrombocytopenic purpura (TTP) is an uncommon microangiopathic disease and often occurs as a complication of systemic lupus erythematous (SLE). However, this probable causal relationship has not been completely proven. The diagnostic differentiation of both diseases is difficult in the first instance because they share similar characteristics that may overlap. We present a case of a 32-year-old woman with antecedents of epilepsy since she was 12 years old. The patient was admitted to the emergency room with a clinical picture of headaches, fever, paleness in the skin and mucosa, confused state, paresthesia, and transient spasticity of the extremities. The laboratory results revealed Coombs negative direct autoimmune hemolytic anaemia, severe thrombocytopenia, significant elevation of the enzyme lactate dehydrogenase, and presence of schistocytes ++ in the peripheral film. In addition, positive antinuclear antibodies and positive anti-native DNA in titers of 1/320 and 1/160, respectively, were found. Renal function was conserved. We concluded that it was a case of TTP associated with SLE and indicated treatment with plasmapheresis and methylprednisolone pulses, obtaining a satisfactory response (normalization of biomarker levels, health condition) after the second session of plasmapheresis. Diagnosis of both SLE and TTP is often difficult to achieve; however, adequate correlation of clinical manifestations and laboratory tests, along with the help of partial therapeutic interventions, may lead to good clinical response.

Lupus nephritis is linked to disease-activity associated expansions and immunity to a gut commensal

Background/PurposeTo search for a transmissible agent involved in lupus pathogenesis, we investigated the faecal microbiota of patients with systemic lupus erythematosus (SLE) for candidate pathobiont(s) and evaluated them for special...

Prognostic Aspects of Lupus Nephritis at Aristide Le Dantec University Hospital in Dakar

Introduction: Kidney injury is common in the course of lupus and affects the functional and vital prognosis. The risk of progression to end-stage renal failure can reach 40% to 60%. Thus we carried out this work for the purpose of an evaluation of the renal and vital prognosis and to deduce the factors of poor prognosis. Patients and method: This was a retrospective, descriptive and analytical study conducted over a period of 10 years from January 1, 2007 to December 31, 2016, performed in the Nephrology Department of Aristide Le Dantec Hospital in Dakar. Patients with lupus nephritis were included. The studied parameters were epidemiological, clinical, paraclinical and progression. We had done a crossover of the patients to look for the factors of poor renal and vital prognosis. Results: Out of 93 cases of lupus patients, 64 were included, a prevalence of 69%. The mean age of the patients was 31.97 ± 10.44 years old. There were 81% women and 19% men, a sex ratio of 0.23. Class III was found in 24 cases (37.5%), Class IV in 20 cases (31.25%), Class V in 15 cases (23.4%), Class II in 4 cases (6.25%) and Class I in 1 case (1.6%). The combination of corticosteroids and immunosuppressants was used in 56.25% of cases. After a follow-up of six months, 19 patients were in complete remission, 21 had resistance and 9 had partial remission. Of the 21 patients who had resistance, 8 were in chronic renal failure. Death was observed in 5 patients and the causes were in 3 patients: pulmonary embolism, bacterial meningitis and pulmonary tuberculosis. The cause of death was unknown in 2 patients. The factors of poor renal prognosis were lymphopenia, the presence of anti-native DNA antibodies, nephrotic syndrome, microscopic hematuria, tubular atrophy and interstitial fibrosis. Risk factors affecting renal survival were the presence of native anti-DNA antibodies, microscopic hematuria, leukocyturia and the presence of a proliferative class. The factors of poor prognosis were renal failure, lymphopenia, nephrotic syndrome, glomerular sclerosis, arteriosclerosis, interstitial infiltration and tubular atrophy. Conclusion: The risk conferred by nephropathy is greater for proliferative glomerulonephritis; it is also correlated with the presence of persistent nephrotic syndrome or severe renal failure.

Hypoventilation alvéolaire sévère révélant un shrinking lung syndrome lupique

The shrinking lung syndrome (SLS) is a rare complication of systemic lupus erythematosus. A 69-year-old man presented with exertional dyspnoea, muscle weakness, and weight loss of 15kg in 6months. Pulmonary function tests revealed a restrictive lung disorder, with a dramatic decrease in maximal inspiratory pressure (17% of theoretical value), and alveolar hypoventilation (pH 7.43; PaCO2 55mmHg). A thoracic CT-scan showed bilateral diaphragmatic elevation. The creatinine phophokinase level was increased at 280U/L. Progress was marked by a rapidly increasing respiratory acidosis (pH 7.24, PaCO2 109mmHg) requiring invasive ventilation. Auto-immune studies revealed positive anti-nuclear antibodies (1/800) and positive anti-native DNA antibody at 45U/L. Treatment with systemic corticosteroids led to an initial improvement but it was not possible to discontinue mechanical ventilation. The outcome was fatal. Autopsy did not reveal any other cause and a diagnosis of the SLS associated with lupus was confirmed. The interesting features of this case report consist of: 1) the presentation of the SLS as an alveolar hypoventilation with a fatal outcome, 2) the presentation of systemic lupus as SLS.

Clinical characteristics during diagnosis of a prospective cohort of patients with systemic lupus erythematosus treated in Spanish Departments of Internal Medicine: The RELES study

IntroductionPatient registries are useful tools for assessing rare diseases. Our objective is to present the Spanish registry of patients with systemic lupus erythematosus (Registro español de pacientes con lupus eritematoso sistémico, RELES). Patients and methodsRELES was started in 2008 as an observational, prospective, multicentre cohort registry that included patients from the time they were diagnosed. The registry's objective is to analyse the incidence and noninflammatory complications of systemic lupus erythematosus (SLE). The departments of internal medicine of 38 Spanish hospitals participate in this registry. ResultsA total of 298 patients with a mean age of 40.8±15.7 years were included, 88.9% of whom were women and 85.6% of whom were white. In the first visit, there was a predominance of joint manifestations (74.5%). One hundred and seventy-seven patients (59.4%) were positive for anti-native DNA. In these patients, there was a higher rate of lupus nephritis (26.7% vs. 14%, p=.009; relative risk [RR], 1.33), haemolytic anaemia (13.6% vs. 4.1%, p=.07; RR, 1.46) and lymphopenia (55.4% vs. 43.8%, p=.05; RR, 1.21). The median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2K) score was 9.64 points (interquartile range, 4–13). The patients treated with antimalarial drugs before the diagnosis of SLE had a median SLEDAI score in the first visit of 5, compared with 8 for those who were not treated with these drugs (p=.02). ConclusionsRELES constitutes the first Spanish patient cohort with SLE recorded from the time of the diagnosis. The presence of anti-DNA has been related to severe manifestations such as nephritis and haemolytic anaemia. Treatment with antimalarial drugs before the diagnosis was associated with less active disease at the initial presentation.

Características clínicas al diagnóstico de una cohorte prospectiva de pacientes con lupus eritematoso sistémico atendidos en servicios de Medicina Interna españoles: estudio RELES

IntroductionPatient registries are useful tools for assessing rare diseases. Our objective is to present the Spanish registry of patients with systemic lupus erythematosus (Registro español de pacientes con lupus eritematoso sistémico, RELES). Patients and methodsRELES was started in 2008 as an observational, prospective, multicentre cohort registry that included patients from the time they were diagnosed. The registry's objective is to analyse the incidence and noninflammatory complications of systemic lupus erythematosus (SLE). The departments of internal medicine of 38 Spanish hospitals participate in this registry. ResultsA total of 298 patients with a mean age of 40.8±15.7 years were included, 88.9% of whom were women and 85.6% of whom were white. In the first visit, there was a predominance of joint manifestations (74.5%). One hundred and seventy-seven patients (59.4%) were positive for anti-native DNA. In these patients, there was a higher rate of lupus nephritis (26.7% vs. 14%, p=.009; relative risk [RR], 1.33), haemolytic anaemia (13.6% vs. 4.1%, p=.07; RR, 1.46) and lymphopenia (55.4% vs. 43.8%, p=.05; RR, 1.21). The median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2K) score was 9.64 points (interquartile range, 4-13). The patients treated with antimalarial drugs before the diagnosis of SLE had a median SLEDAI score in the first visit of 5, compared with 8 for those who were not treated with these drugs (p=.02). ConclusionsRELES constitutes the first Spanish patient cohort with SLE recorded from the time of the diagnosis. The presence of anti-DNA has been related to severe manifestations such as nephritis and haemolytic anaemia. Treatment with antimalarial drugs before the diagnosis was associated with less active disease at the initial presentation.

RESULTS OF AN OBSERVATIONAL PROSPECTIVE STUDY OF THE EFFICACY AND SAFETY OF BELIMUMAB (BENLYSTA®) IN SYSTEMIC LUPUS ERYTHEMATOSUS IN REAL CLINICAL PRACTICE

Therapy for systemic lupus erythematosus (SLE) remains challenging. The long-term use of glucocorticoids (GC) and cytostatics considerably improves life expectancy, but at the same time favors the development of irreversible organ damages. To evaluate the efficacy of belimumab (BLM), a biological agent, that blocks B-lymphocyte-stimulating factor registered for the treatment of active SLE, is an important task of the practice of rheumatology. Objective: to evaluate the efficacy and safety of BLM in patients with high and moderate SLE activity. Subjects and methods. The investigation enrolled 16 patients with a Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) score of 6 to 19, who were positive for antinuclear factor (100%) and had low complement levels and high anti-native DNA antibodies (81%). BLM was used as monthly intravenous infusions at a dose of 10 mg/kg. The efficiency and safety of the therapy were evaluated monthly and 1 year after the initiation of treatment with BLM; SLE activity was estimated using SLEDAI-2K; a physician’s global assessment of disease activity on a visual analogue scale (VAS); anti-DNA antibody level changes, complement levels, a GC dose, damage index, and adverse events were determined. Results and discussion. BLM therapy proved to be effective in 62% of cases at 1 year after therapy initiation. At 1 month, SLE activity significantly decreased with SLEDAI-2K score diminishment from 9.31±3.21 to 6.25±2.80 in the entire group (p < 0.04). Over a month, the physician’s global assessment of disease activity significantly reduced from 19.25±6.60 to 13.68±3.97 mm (р<0.01) and reached minimum (8.28±6.87 mm) by 10 months of therapy. There was a significant decrease in anti-DNA antibodies and an increase in complement C4 level at 5 and 3 months of therapy, respectively. Six of the 10 patients who had received a complete cycle of BLM therapy achieved remission at 12 months. The dose of GC was significantly reduced at 6 months of therapy. Adverse events were rare. BLM was discontinued because of its inadequate efficacy in 4 patients. Conclusion. Twelve-month therapy with BLM is effective in patients with high and moderate SLE activity according to SLEDAI-2K and with high immunological activity. The use of BLM in SLE contributes to a GC dose reduction and fails to cause serious adverse events.

English

The main objective of this study was to focus on the relationship of nDNA antibodies with rheumatoid arthritis (RA) and to determine the specificity, sensitivity, positive predictive value and negative predictive value of nDNA for the clinical diagnosis of rheumatoid arthritis. The study included a total of 40 rheumatoid arthritis cases that fulfilled the American College of Rheumatology (ACR) diagnosis criteria for rheumatoid arthritis as well as 40 age and sex matched controls. Agglutination technique was used for qualitative and semi-quantitative measure of rheumatoid factor (RF) and indirect immunofluorescence assay was employed for the determination of anti-nDNA antibodies. RF latex agglutination test was carried out to confirm RA cases, out of which four (10%) turned out to be negative, so only 36 RA cases were further investigated and analyzed through indirect immunofluorescence assay. Out of 36 individuals, 31 (86%) were negative, three (8.3%) were strong positive and two (5.5%) were weak positive. No significant association was found between nDNA antibodies and rheumatoid arthritis disease. Keywords: Rheumatoid arthritis, anti-native DNA antibodies, immunofluorescence assay, sensitivity, positive predictive value, negative predictive value. African Journal of Biotechnology , Vol 13(38) 3943-3949

Connective tissue diseases in hospital practice in Ouagadougou (Burkina Faso)

To describe the semiological and immunological features of connective tissue diseases seen at the Yalgado Ouédraogo University Hospital in Ouagadougou. A retrospective study reviewed the records of patients seen in the hospital dermatology and internal medicine departments from January 1, 2004, through December 31, 2009 and diagnosed with systemic lupus erythematosus (SLE), systemic sclerosis (ScS), dermatopolymyositis (DPM), primary Gougerot-Sjögren disease (GS), polymyositis (PM) or indeterminate connective tissue disease (ICTD) meeting the criteria of the American College of Rheumatology. The study included 42 patients, 36 women and 6 men. Their mean age was 41.2 years ±11.97 (range: 15-75). SLE was the diagnosis for 10 patients, ScS for 14, DPM for 7, primary GS for 1, PM for 1, and ICTD for 9. Hematologic (93%), cutaneous (88%), and rheumatologic (81%) abnormalities were the most frequent manifestations. The specific auto-antibodies associated with SLE patients were: anti-native DNA (3/6), anti-Sm (3/6), anti-RNP (3/6), and anti-SSA (4/6); anti-Scl 70 antibodies were present in 5 patients with ScS. Connective tissue diseases seem to be rare in Africa, south of the Sahara. However, the very fragmentary studies and the weak healthcare coverage do not allow any definitive conclusions.

Prévalence et valeur diagnostique des anticorps antinucléaires de spécificité antigénique indéterminée : étude rétrospective à propos d’une série de 90 patients

PurposeThe objective of this study was to determine the clinical relevance and the diagnostic significance of positive antinuclear antibodies (ANA) without identified antigenic target by the usual characterization technique. Patients and methodsRetrospective study conducted in the Laboratory of Immunology of Habib Bourguiba Hospital (Sfax, Tunisia) during 18months. The inclusion criteria were the presence of an ANA titer greater or equal to 1/320 with negative characterization result. ANA screening was performed by indirect immunofluorescence (IIF) on Hep2 cells. Each positive serum was tested by IIF on Crithidia luciliae (anti-native DNA) and by immunodot (anti-nucleosome, anti-histone, anti-Sm, anti-RNP, anti-SSA, anti-SSB, anti-Scl 70, anti-PM-Scl, anti-Jo1, anti-PCNA and anti-ribosomal protein). Sera of systemic lupus erythematosus (SLE), myositis, and scleroderma patients were tested for anti-Ku, anti-PL7, anti-PL12 and anti-Ro-52 using dot myositis. ResultsSera of 90 patients were studied: 18 men and 72 women (average age: 44years). Drug-induced ANA was found in eight patients. The most frequent clinical symptoms were joint (56.7%), cutaneous (54.4%) and constitutional symptoms (45.6%). The diagnosis of an autoimmune disease was suspected in 49 patients (54.5%) and confirmed in 30 (33.3%) including 20 cases of connective tissue disease: myositis (n=6), scleroderma (n=5), Sjögren's syndrome (n=3), SLE (n=4), rheumatoid arthritis (n=6) and antiphospholipid syndrome (n=4). Other autoimmune diseases were less frequent. The anti-Ku antibody was detected in the majority of patients with connective tissue disease. The diagnosis of non-autoimmune diseases was established in 25.5% of patients. Eighteen patients (20%) had no diagnosis orientation. ConclusionOur study demonstrated the diagnostic value of the presence of ANA even in the absence of known antigenic target, confirmed the role of the IIF as “gold standard” test for ANA screening, and suggested the usefulness of the addition of Ku antigen in the immunodot classic profile.

The main stages in the history of systemic lupus erythematosus

Systemic lupus erythematosus can be considered the most characteristic and important among the connective tissue diseases. In this short review the main stages of its history are sketched, from the introduction of the term "lupus", traditionally attributed to Roger Frugardi, in 1230 (but in fact already documented in the 10th century) to the actual knowledge of its clinical and laboratory aspects. Initially considered exclusively of dermatological interest, the first to describe a systemic form with visceral involvement were Moriz Kohn Kaposi and William Osler. Significant contribution was also given by serological diagnosis, and in particular, by the identification of specific markers of disease, such as anti-native DNA and anti-Sm antibodies, allowing early diagnosis and the establishment of an adequate therapy.

Drug-Induced Autoimmune-Like Hepatitis: A Case of Chronic Course After Drug Withdrawal

Dear Editor, We read with interest the review by Albert J. Czaja on drug-induced autoimmune-like hepatitis [1]. As underlined by the author, the outcome is usually favourable after drug withdrawal, either spontaneously or after a few months of corticosteroid therapy. In contrast with classical autoimmune hepatitis, drug-induced disease does not require longterm immunosuppressive treatment [1, 2]. We report here a rare exception to this rule in a patient with minocyclineinduced autoimmune-like hepatitis which self-perpetuates after drug withdrawal. A 17-year-old male patient was treated for acne vulgaris with minocycline 100 mg/day for 2 months, then 50 mg/day for 1 month from August to October 2005. He had no previous history of liver disease, intravenous drug or alcohol abuse. His liver blood tests controlled 2 years before were in the normal range. At the end of minocycline treatment, a laboratory workup was performed and showed elevated serum levels of alanine aminotransferase (ALT 464 IU/l, normal \ 46), aspartate aminotransferase (AST 293 IU/l, normal \ 49), gamma-glutamyl transpeptidase (GGT 188 UI/l, normal \ 88), alkaline phosphatase (AP 343 UI/l, normal \ 290) and normal bilirubin level (11 lmol/l). His prothrombin index was 67% and gammaglobulins were elevated (31 g/l). The blood eosinophil count rose to 804/ll. Anti-nuclear and anti-smooth muscle antibodies were positive at a titre of 1/6,400 and 1/400, respectively, whereas anti-liver/kidney microsomal and anti-mitochondria antibodies were negative. Anti-native DNA antibodies were slightly positive using the Farr test (6 IU/ml, normal \ 4). Serologies for hepatitis A, B, C, Epstein-Barr virus and cytomegalovirus were negative. Abdominal ultrasound sonography was normal. A liver biopsy was performed and showed features of chronic hepatitis with portal and lobular lymphoplasmocytic infiltrate, rosette formation, peacemeal necrosis and centralportal bridging necrosis. In addition, bile duct damage with lymphocytic cholangitis and ductular proliferation were observed. The diagnosis of auto-immune hepatitis induced by minocycline was made. Treatment with prednisone 40 mg/day was initiated. Serum aminotransferases normalised within 1 month. Prednisone was gradually reduced and stopped after 4 months. Three months later, there was a relapse with serum ALT level of 105 IU/l, AST of 73 IU/l and GGT of 104 IU/l. Gamma globulins were elevated (25 g/l). Prednisone was reintroduced at 30 mg/day with azathioprine 125 mg/day. On the basis of histological bile duct damage, ursodeoxycholic acid 1,000 mg/day was added. His serum levels of aminotransferases and GGT returned to normal within 3 months. Prednisone was stopped after 6 months and the patient was maintained on azathioprine and ursodeoxycholic acid. From 2007 to 2009, periods of poor compliance translated into transient increased levels of aminotransferases. In October 2010, the liver tests were normal. The prothrombin index was 88% and serum albumin was 41 g/l. However, immunological abnormalities were still present. Serum immunoglobulin G was elevated (21.3 g/l). Anti-nuclear and anti-smooth muscle antibodies were positive at titres of 1/3,200 and 1/400, respectively. Anti-native DNA antibodies were positive (50 IU/ml, normal \ 4). During the following 2-month period, the compliance rate was very poor, i.e. less A. Heurgue-Berlot (&) B. Bernard-Chabert G. Thiefin Department of Hepato-Gastroenterology, CHU Reims, Reims, France e-mail: aheurgue@chu-reims.fr

Humanized SCID Mice Models of SLE

The pathological DNA-specific B cells in Systemic lupus erythematosus are a logical target for a selected therapeutic intervention. It has been recently shown that complement receptor type 1 on human B and T-lymphocytes has suppressive activity. The co-crosslinking of this receptor with the B-cell receptor (BCR) inhibits B cell activation and proliferation and it could be an attractive new target for negative signal delivery. Experimental therapy in humans is limited by many restrictions. Severe combined immunodeficiency (SCID) mice, which lack both T and B lymphocytes and accept xenogenic cells have been used for human cell transfer for evaluating the pathogenesis of human SLE. We hypothesize that it may be possible to re-establish tolerance to native DNA in humanized SCID mice with cells transferred from SLE patients by administering to them a chimeric molecule, containing a monoclonal antibody against human inhibitory complement receptor type 1 coupled to a decapeptide DWEYSVWLSN that mimics DNA antigenically. These protein-engineered molecules are able to co-crosslink selectively the antigen receptors of B-cells possessing anti-native DNA specificity with the inhibitory surface receptors, thus delivering a strong suppressive signal.