Normal C4 Levels Research Articles

Low C3 Serum Levels Predict Severe Forms of STEC-HUS With Neurologic Involvement.

Background: The correlation between the severity of hemolytic uremic syndrome related to Shiga toxin–producing Escherichia coli (STEC-HUS) and involvement of the complement system has been examined in a small number of studies, with conflicting results. In the present study, we investigated whether serum C3 levels on admission are associated with neurologic involvement.Methods: To this purpose, 68 consecutive STEC-HUS patients were recruited and main clinical and laboratory variables ad hospital admission were compared between those with or without neurologic involvement.Results: STEC-HUS patients who developed neurologic involvement (NI) showed significant higher leukocyte count, C-reactive protein and hemoglobin, and lower sodium levels as compared with those without. Interestingly, baseline serum levels of C3 were significantly lower in patients with NI as compared with those without (p < 0.001). Moreover, when stratified according to need of Eculizumab rescue therapy due to severe NI, patients treated with this drug showed baseline C3 serum levels significantly lower than those who were not (p < 0.001).Low C3 was independent risk factor for NI in our patients' population when entered as covariate in a multivariate logistic regression analysis including other major variables previously proposed as possible predictors of poor prognosis in STEC-HUS (for instance, leukocyte count, c-reactive protein, sodium levels) (HR 6.401, 95%CI 1.617–25.334, p = 0.008 for C3).To underline the role of complement in the worsening of STEC-HUS patients' clinical conditions and outcomes, all patients were divided into two groups according to the baseline lower vs. normal serum levels of C3 and the main data on care needs were assessed. Interestingly more patients with lower C3 serum levels required renal replacement therapy (p = 0.024), anti-hypertensive therapy (p = 0.011), Intensive Care Unit admission (p = 0.009), and longer hospitalization (p = 0.003), thus displaying significantly more severe disease features as compared with those with normal C3 serum levels.Conclusions: Our data suggests that children with STEC-HUS with decreased C3 concentrations at admission are more likely to develop neurologic involvement and are at increased risk of having severe clinical complications.

P0455CLINICAL PROFILE OF C3 GLOMERULOPATHY AT A TERTIARY CARE CENTRE

Abstract Background and Aims To study the clinico-pathological profile of patients with C3 glomerulonephritis at a tertiary care entre. Method A prospective observational study of all cases of C3 glomerulonephritis was done between August 2016 and December 2017. C3 glomerulonephritis was defined by predominant glomerular C3 fragment deposition with electron-dense deposits on EM Results Total of the 1190 patients under went biopsy during the study period. C3 glomerulonephritis was present in 32 cases (2.68%). The mean age was 35±2 years. Out of the 32 patients, 18 were male ( 56.25% ) and 14 were female (43.75% ). Hypertension was present in 30 out of 32 patients (93.7%) while diabetes was present in 7 patients (21.8%). Most common presentation was with RPGN (72%). 100% patients had active urinary sediments. The mean serum creatinine at admission was 5.15mg/dl while it was 3.18mg/dl at discharge. The mean serum C3 was 83.8 mg/dl with 18 patients (56.25%) having low serum C3 levels in our study. All patients had normal serum C4 levels with mean being 29.34 mg/dl. Anti CFH antibody titres were measured in 6 patients of with it was elevated in 2 patients (33.3%). On LM, 14 out of 32 had crescentic GN (43.75%), 12 had diffuse exudative pattern (37.5%), 4 had diffuse mesangioproliferative pattern (12.5%), 3 had MPGN pattern (9.37%), 3 had focal exudative pattern (9.37%), 1 patient had glomerular TMA (3.15%) and 1had chronic sclerosing pattern ( 3.15%). On IF, all patients had dominant C3 staining. Also 3 (9.37%) patients had IgG staining of 1+ intensity. EM study was done in two patients and was suggestive of DDD in one patient (3.15%). All patients were managed with pulse steroids followed by oral steroids. IV Cyclophosphamide was used monthly for 6 doses in 14 patients ( 43.7%) while oral cyclophosphamide was used in 2 patients (6.25%). Plasmapharesis was done in 11 patients (34.37%) and 11 patients required haemodialysis (34.37%) Conclusion C3 glomerulonephritis has emerged as a new entity in the recent past with significant percentage of our patients presenting with RPGN. Hypertension was present in most patients. On light microscopy, the most common presentation was crescentic glomerulonephritis, One third of our patients had advanced renal failure requiring haemodialysis. Plasmapharesis was done in one third of patients.

P0181PERSISTENT C3 HYPOCOMPLEMENTEMIA AND MODERATE TUBULOINTERSTITIAL SCARRING AS EARLY PREDICTORS OF END-STAGE RENAL DISEASE IN LUPUS NEPHRITIS

Abstract Background and Aims The prognosis of lupus nephritis (LN) has become progressively more favorable thanks to the introduction of cyclophosphamide and mycophenolate as the mainstay of induction of remission treatment regimens. However, 10-15% of patients still progress to end-stage renal disease (ESRD). Early predictors of ESRD, i.e. in the first six months between kidney biopsy and the completion of induction, are currently limited to few histological and clinical features: ≥ 25% interstitial fibrosis and tubular atrophy (IFTA), fibrinoid necrosis, fibrous crescents, and thrombotic microangiopathy (TMA) [Rijnink EC et al CJASN 2017; Song D Arthritis Res Ther 2013]; lack of decrease in proteinuria &amp;lt; 0.5 g/24-h at 3 and 6 months from kidney biopsy [Tamirou F Ann Rheum Dis 2016], baseline GFR ≤ 90 ml/min/1.73 m2, lack of decrease in urinary protein-to-creatinine ratio (UPCR) &amp;lt; 1 and anti-dsDNA positivity at the end of induction [Dall’Era M Lupus Sci Med 2015]. In this study we sought to identify further clinical and histological predictors of ESRD in LN. Methods Adult patients diagnosed with LN between 1995 and 2018 in two centers (NIAMS, Bethesda, Maryland, USA, and Nefrologia, AOU di Parma, Italy) were retrospectively identified. Patients with available serum C3 and C4 levels at the time of biopsy and 6 months thereafter, and a follow-up of at least 6 months, were included. Baseline and follow-up data (until March 2019) including age, sex, ethnicity, clinical, histological and laboratory findings were collected. Histology slides were reviewed by an experienced renal pathologist and biopsies re-scored using the ISN/RPS classification and NIH activity and chronicity indices. Distinct histological features were assessed individually (e.g. TMA). Persistent C3 hypocomplementemia was defined as decreased serum C3 levels at the time of biopsy and after 6 months (i.e. after the completion of induction), with concurrent normal serum C4 levels at 6 months. Early renal recovery was defined as either an increase in eGFR above 60 in those with a baseline eGFR &amp;lt; 60 ml/min/1.73 m2, or a 50% decrease in proteinuria in those with a baseline eGFR ≥ 60 ml/min/1.73 m2 and ≥ 0.5 g/24-h or g/g UPCR at the time of biopsy. Variables were tested for their predictive power of death-censored ESRD in univariate and multivariate Cox regression models. Results 74 patients (NIAMS n = 36; Parma n = 38) met our criteria. Median follow-up duration was 64 months (range 6-230). On univariate analysis, the following parameters predicted ESRD: Hispanic ethnicity; age at biopsy; persistent C3 hypocomplementemia; normalization of both C3 and C4; renal recovery after induction; NIH activity index; presence of TMA; ≥ 25% IFTA. Multivariate Cox regression models for ESRD were created considering statistically significant variables (p &amp;lt; 0.05). In a model including Hispanic ethnicity, age at biopsy, and persistent C3 hypocomplementemia, the latter predicted ESRD with an HR of 5.22 (95% CI [1.33, 20.58] p = 0.018) when adjusting for renal recovery after induction. Upon including histological features in the model, persistent C3 hypocomplementemia, TMA, and the NIH activity index lost significance, while ≥ 25% IFTA predicted ESRD with an HR of 27.26 (95% CI [2.12, 350.54], p = 0.011). Conclusion In patients with LN, ≥ 25% IFTA at baseline biopsy is a predictor of ESRD, allowing for early risk stratification with the potential of informing treatment strategies. Where percent IFTA is unavailable or its assessment unreliable (e.g. inadequate biopsy specimen for tubulointerstitial assessment), persistent C3 hypocomplementemia represents a reliable and reproducible early predictor of ESRD, irrespective of early renal recovery after induction.

Quality of life and influencing factors of patients with rheumatoid arthritis in Northeast China

PurposeRheumatoid arthritis (RA) is a disease with a high disability rate, resulting in severe family and social burden. The aim of treatment is to improve the health-related quality of life (QoL) of patients. The purpose of this study was to evaluate the QoL of patients with RA in Northeast China and analyze its influencing factors.MethodsThe study group consisted of 200 patients diagnosed with RA. The control group consisted of 200 healthy subjects. All subjects were residents in Northeast China. The investigation was conducted by questionnaire survey and electronic medical record. The WHOQOL-BREF, The Short-Form 36 Health Survey (SF-36) and Quality of Life Instruments for Chronic Diseases-RA (QLICD-RA) were used as questionnaires.ResultsThe QoL scores acquired by SF-36, WHOQOL-BREF and QLICD-RA scales showed significant differences between RA and control groups (P < 0.001). Multiple regression analysis showed that sleep duration (P = 0.001), psychological counseling (P < 0.001) and C4 level (P = 0.001) influenced the SF-36 scale evaluation model. IgA levels (P < 0.001) and being overweight (P = 0.030) were included in the WHOQOL-BREF evaluation model. Adequate sleep (P = 0.001) and psychological counseling(P = 0.050) entered the QLICD-RA scale evaluation model (P = 0.050), in which psychological counseling, normal C4 levels and being overweight were protective factors for RA, insufficient sleep and IgA levels were risk factors for RA.ConclusionsThe QoL of RA patients is generally lower than those of healthy subjects in the Northeast China, Northeast China. Sleep duration, BMI (Body mass index), psychological counseling, C4 and IgA levels are factors that influence the QoL scores of RA patients.

Prevalence and risk factors for gallstone disease: A population‐based cross‐sectional study

To explore the prevalence of and risk factors for gallstone disease in Shanghai, China. A population-based cross-sectional study was conducted in Shanghai between 2016 and 2017. Using a three-stage stratified sampling strategy, 4009 participants (1753 men and 2256 women) from 10 districts were enrolled. The overall prevalence of gallstones was 6.83% (6.22% for men vs 7.31% for women, P = 0.173). According to the multivariate analysis, individuals aged ≥40 years (odds ratio [OR] 3.058, 95% confidence interval [CI] 2.110-4.433, P < 0.001), hypertension (OR 1.479, 95% CI 1.076-2.034, P = 0.016), thyroid disease (OR 1.409, 95% CI 1.029-1.928, P = 0.032), a family history of gallstones (OR 2.234, 95% CI 1.362-3.662, P = 0.001) and a waist-to-height ratio ≥0.5 (OR 1.656, 95% CI 1.197-2.292, P = 0.002) had an increased risk of developing gallstones. The risk of gallstone disease was 2.232 (95% CI 1.167-4.268, P = 0.015) times higher in individuals with elevated C4 levels than in those with normal C4 levels. Diabetes (OR 4.144, 95% CI 1.171-14.671, P = 0.028) was a risk factor for the formation of gallstones with diameters ≥1 cm, and men were more susceptible to develop multiple stones (OR 2.356, 95% CI 1.321-4.200, P = 0.004). Individuals aged ≥40 years, with a history of hypertension and familial gallstones, a high waist-to-height ratio, thyroid disease and high C4 levels were related to an increased risk of gallstone disease.

Perplexing Etiology of Acute Retinal Necrosis in a Renal Transplant Recipient.

Atypical hemolytic uremic syndrome is a rare form of thrombotic microangiopathy caused by complement pathogenic variants. We describe a case of a 33-year-old woman who presented as rapidly progressing renal failure requiring dialysis and had anemia, microhematuria, low C3, normal C4 levels, and normal platelet count. Renal biopsy revealed arteriolar thrombotic microangiopathy and acute tubular injury. Patient was treated with plasma exchange and hemodialysis as required. This resulted in partial recovery at 1 month. Genetic workup by multiplex ligation-dependent probe amplification revealed a 1.5 times higher signal intensity on downstream region of CFH gene and 50% reduced intensity of exon 6 of CFHR1 gene, suggesting a gene conversion event, similar to those previously reported from Spain and Portugal.

Immune status of splenectomized patients following vaccination against encapsulated bacteria

Aim: The current study aimed to observe the effectiveness of a pneumococcal vaccine and a Haemophilus influenzae vaccine in splenectomized patients by quantification of serum antibody and complement levels, analysis of T and B lymphocytes with flow-cytometry and determination of the percentage of Natural Killer cells and the CD4+ to the CD8+ lymphocyte ratio.Material and Methods: The study included 22 adult patients who had undergone splenectomy between May 1999 and December 2006. The Pneumo-23 vaccine was administered for protection against Streptococcus pneumonia to all patients, whereas the Act-HIB vaccine was administered for protection against Haemophilus influenzae type B to 12 patients after January 2002.Hemogram, IgG and IgM antibody concentrations, serum levels of Complement protein 3 and Complement Protein 4 were obtained and lymphocytes were analyzed whether they were CD3+ and CD19+ by flow cytometry. At the second time point, in 2009, CD4+/CD8+ T-cell ratio and the percentage of CD3/CD16+CD56 Natural Killer cells were evaluated in addition to aforementioned parameters.Results: All of the study patients had normal IgG levels. Three patients had low levels of IgM. C3 and C4 values were normal. Ten patients showed a low CD3+ T-cell distribution at 5 years. The percentage of CD19+ B-lymphocytes returned to normal. Sustained suppression of CD19 level was observed only in one patient with immune thrombocytopenic purpura. CD8 distribution was normal in all patients. At 5 years, reduced CD4 percentage was detected in 5 patients with immune thrombocytopenic purpura, 3 of whom had suppressed levels of Natural Killer cells concomitantly. Normal levels of IgG, C3, C4 and CD19+ B-cell percentages were found at the final laboratory assessment for all patients.Conclusion: Our findings indicate that immunological functions are restored following administration of the Pneumo-23 and Act-HIB vaccines. Further studies are needed to obtain a prognostic immune profile index that could help predict patients at high risk for post-splenectomy sepsis.

Serum sickness-like reaction to a second generation antipsychotic drug

Introduction: Serum sickness is a type III hypersensitivity reaction. Immune complex deposition activates complement pathways resulting in fever, vasculitic rash, arthritis and lymphadenopathy. Medications are known to trigger serum sickness-like reactions which clinically resemble serum sickness, however, are not thought to involve circulating immune complexes. The full pathophysiology is not clear. Risperidone is an atypical antipsychotic drug commonly used in the paediatric population. Aim: To describe the diagnosis, disease course and outcome of a patient who developed serum sickness-like reaction secondary to risperidone. Methods: Review of patient chart and medical interview in accordance with institutional research ethics board approval. Results: The patient, a 7 year old male with Attention Deficit Hyperactivity Disorder, was started on risperidone 0.25 mg once daily. Within a week the dose was increased to 0.5 mg once daily. During the third week after initiation of medication, the patient developed generalized purpuric, confluent, maculopapular rash. Although the patient did not have any signs and symptoms of a viral illness, he was diagnosed with viral-induced exanthema and continued on risperidone. On day 28, he developed significant, bilateral swelling of upper and lower extremities, facial angioedema, lymphadenopathy, arthralgia and arthritis in ankles, knees, hands and elbows without fever. Investigations showed normal complement C3 and C4 levels. C1 esterase inhibitor, anti-nuclear antibody and urinalysis were normal. Erythrocyte sedimentation rate, C-reactive protein and leukocyte levels were elevated. The diagnosis of serum sickness-like reaction to risperidone was made and the patient subsequently treated with cetirizine, hydrocortisone, and prednisone for 1 week with significant improvement. Skin biopsy was declined by the patients’ parents and therefore was not performed. Provocative oral challenge to risperidone was not considered because of clear suggestive history and ethical consideration. Conclusion: Psychotropic medications are known to cause cutaneous eruptions. Serum sickness-like reactions can happen upon exposure to risperidone. Clinicians should be aware of this potential adverse reaction that can develop weeks after therapy initiation, and be encouraged to discontinue risperidone when the suggestive symptoms emerges. Statement of novelty: We describe a case of serum sickness-like reaction to risperidone in a paediatric patient. To our knowledge, this is the first case of serum sickness-like reaction to risperidone.

The Role of Monitoring Complement Levels in Catastrophic Antiphospholipid Syndrome: A Case Series of 4 Patients

Introduction: Catastrophic antiphospholipid syndrome (CAPS) is characterized by multiple intravascular thrombotic events occurring over a short time period in the presence of persistently detectable antiphospholipid antibodies (APLA). Despite its clinical significance with mortality rate of 40-50%, the underlying pathophysiology remains somewhat enigmatic. More recent focus on the complement system as it interacts with the coagulation cascade has led to off-label use of eculizumab, a humanized monoclonal antibody against C5, in the treatment of CAPS. Consequently, monitoring of disease status with complement levels is an area of interest. We report complement levels in four patients with CAPS who had various clinical outcomes. Methods: Four patients admitted to SUNY Upstate Medical University with CAPS between February and May 2019 were included in this case series. All patients had APS with prior history of refractory CAPS (persistent disease despite standard therapy with steroids, rituximab, and therapeutic plasma exchange [TPEX]). Antiphospholipid antibodies (APLA) and complement (C3 and C4) levels were monitored during admission until discharge or death. Results: Patient characteristics are summarized in Table 1. Patient 1 was a 42-year-old female with antiphospholipid syndrome (APS) on warfarin, ischemic stroke, and aortic valve replacement admitted on March 2019 with shortness of breath, hemoptysis and menorrhagia. She was found to have elevated APLA, thrombocytopenia, and acute renal failure with renal biopsy confirming APS nephropathy. Despite therapy with ongoing anticoagulation, steroids, rituximab, IVIG, and TPEX her clinical course continued to deteriorate. Hypocomplementemia was present (both low C3 and C4), with lowest C3 level on admission at 31 (Graph 1A). Decision was made to pursue eculizumab on 4/16/19 with continued clinical decline and no improvement in complement levels. She ultimately died on 4/24/19. Patient 2 was a 35-year-old male with systemic lupus erythematosus (SLE), APS, end-stage renal disease, and Libman-Sacks endocarditis status post bioprosthetic aortic valve replacement admitted in February 2019 for worsening digital ischemia. Workup showed presence of lupus anticoagulant, thrombocytopenia, low C3 levels (Graph 1B), normal C4 levels, and arterial thrombi in the upper and lower extremities. Prior to initiation of treatment, respiratory status declined due to massive pulmonary embolus. He died after PEA arrest shortly thereafter. Patient 3 is a 63-year-old male with chronic ITP and APS on warfarin, maintenance rituximab and intermittent apheresis admitted with worsening renal dysfunction in April 2019. Workup demonstrated acute on chronic thrombocytopenia, elevated APLA, and normal C3 and C4 levels (Graph 1C). Renal replacement therapy was commenced and he was discharged to receive ongoing outpatient therapy. Patient 4 is a 35-year-old male with history of SLE and APS admitted in April 2019 with renal failure, anemia and thrombocytopenia. Workup showed presence of APLA. Despite therapy with steroids, IVIG, rituximab and TPEX he became anuric with renal biopsy showing thrombotic microangiopathy. He was also bacteremic with a mitral valve vegetation for which he underwent valve replacement. Hospital course was complicated by need respiratory failure necessitating intubation and ECMO. C3 levels were consistently low, but varied throughout his long admission (Graph 1D) and were not necessarily related to his clinical course (sepsis, ECMO, etc.). C4 levels were normal. Conclusions: Complement levels were variable among the patients in this case series. Three out of four patient had low C3, while only one patient had low C4. Further, complement levels did not improve in one patient after administration of eculizumab. Routine laboratory testing for C3 and C4 may not be optimal assays for monitoring disease status in CAPS. More specialized complement testing, such a C5 a/b, may be more appropriate especially in the setting of eculizumab use. While eculizumab is typically used in refractory disease, it may be pertinent to move this therapy into early line treatment to achieve better outcomes in certain clinical scenarios. Identification of a more specific biomarker to recognize cases in need of early therapy is warranted. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Eculizumab, a humanized monoclonal IgG antibody that binds to complement protein C5, is discussed for its off-label use in the treatment of catastrophic antiphospholipid antibody syndrome.

Investigation of alanine, propionylcarnitine (C3) and 3-hydroxyisovalerylcarnitine (C5-OH) levels in patients with partial biotinidase deficiency

Abstract Background Biotinidase deficiency is a treatable metabolic disease that can be seen with various neurological and dermatological complications. Biomarkers such as alanine, propionylcarnitine (C3) and 3-hydroxyisovalerylcarnitine (C5-OH), which are used to diagnose biotinidase deficiency, are also present. Materials and methods In cases with partial biotinidase deficiency and normal biotinidase activity, alanine, C3 and C5-OH levels were compared in the field by liquid chromatography-tandem mass spectrometry. Results There was no significant difference between subjects with partial biotinidase deficiency and those with normal biotinidase activity between C3 and C5-OH levels. The mean alanine levels in heel blood and plasma were significantly higher than those with normal biotinidase activity in patients with partial biotinidase deficiency. Conclusion In cases with partial biotinidase deficiency, the heel blood alanine level that can be detected in the neonatal screening program may be a leading marker in diagnosis.

Lupus enteritis as the only active manifestation of systemic lupus erythematosus: A case report

BACKGROUNDLupus enteritis is a rare manifestation of systemic lupus erythematosus (SLE). Diagnosis of this condition is difficult, especially in the absence of other symptoms related to active SLE. We present the case of a 25-year-old female with lupus enteritis as the sole initial manifestation of active SLE.CASE SUMMARYA 25-year-old African American female presented to the Emergency Department complaining of diffuse abdominal pain, diarrhea, nausea, and vomiting for 2 days. Her past medical history was significant for seasonal allergies and family history was pertinent for discoid lupus in her father and SLE in a cousin. The patient’s vital signs on presentation were normal. Her physical exam was remarkable for significant lower abdominal tenderness without guarding or rigidity. A computed tomography of the abdomen and pelvis revealed marked circumferential wall thickening and edema of the proximal and mid small bowel predominantly involving the submucosa. Our main differential diagnoses were intestinal angioedema and mesenteric vein thrombosis. However, mesenteric vessels were patent, and laboratory testing for hereditary angioedema showed a normal C1 Esterase Inhibitor level and low C3 and C4 levels. Infectious work-up was negative. Autoimmune tests showed elevated anti-nuclear antibodies (ANA) (13.6), anti-Smith antibody, and anti-ribonucleoprotein (anti-RNP) antibody. The patient was diagnosed with SLE enteritis. She was maintained on bowel rest, given intravenous hydration, and started on methylprednisolone 60 mg IV daily. She had significant improvement in her abdominal pain, diarrhea, and emesis after 2 days of treatment. Steroids were tapered and maintained on Hydroxychloroquine with no relapses one year after presentation.CONCLUSIONThis case of lupus enteritis represents a rare manifestation of SLE. Diagnosis requires clinical suspicion, characteristic imaging and laboratory tests. Endoscopic appearance and biopsies usually yield non-specific findings. High dose steroids are the preferred treatment modality for moderate and severe cases.

Lupus Enteritis as the Only Manifestation of Active Systemic Lupus Erythematosus

Lupus enteritis is a rare manifestation of systemic lupus erythematosus (SLE). It is a difficult diagnosis to make, especially in the absence of other symptoms related to active SLE. We present a case of a 25 year old female who presented with lupus enteritis as the sole manifestation of active SLE. A 25 year old female presented to the ED with diffuse abdominal pain, diarrhea, nausea, and vomiting for 2 days. She had a medical history of seasonal allergies. Family history was significant for SLE in her cousin. Her vital signs were normal, and physical exam revealed lower abdominal tenderness. A CT of the abdomen showed marked circumferential wall thickening and edema of the proximal and mid small bowel loops predominantly involving the submucosa (Image 1). Our main differential diagnoses were intestinal angioedema and mesenteric vein thrombosis. The mesenteric vessels were patent and without evidence of thrombosis. Infectious workup was negative. Laboratory testing for hereditary angioedema showed a normal C1 Esterase Inhibitor level and low C3 and C4 levels. Autoimmune work-up showed elevated ANA (13.6), anti-Smith antibody (ab), and anti-RNP ab (Table 1). The patient was diagnosed with SLE enteritis. She was maintained on bowel rest, given intravenous (IV) hydration, and started on methylprednisolone 60 mg IV daily. She had significant improvement of all her symptoms and was discharged on prednisone 75 mg by mouth daily. In SLE, isolated gastrointestinal activity without other organ involvement is highly unusual. Lupus enteritis presents with non-specific symptoms, making the diagnosis difficult. Nevertheless, it is important to identify this disease manifestation as the mortality among patients with SLE with acute abdominal pain is approximately 11%. Lupus enteritis causes submucosal edema of the jejunum and ileum. The classic findings on CT scan include circumferential bowel wall thickening (“target sign”), dilation of intestinal segments, and engorgement of mesenteric vessels (“comb sign”). The CT scan in our case showed the “target sign”. Given her negative work up for hereditary angioedema and her family history of lupus, we decided to test for SLE. We did not perform an upper endoscopy because it often does not contribute to diagnosis. It's important to note that while most sources advocate pulse dose steroids, we were able to achieve symptomatic control with methylprednisolone 60 mg daily.2543_A Figure 1. Ab (antibody); ANA (anti-nuclear antibodies); dsDNA (double-stranded DNA); Anti-RNP (anti-ribonucleoprotein).2543_B Figure 2. Image 1. Marked circumferential wall thickening consistent with “target sign” involving multiple loops of proximal/mid small bowel. There is predominantly submucosal thickening/edema, more predominantly in the mid abdomen. The thickened small bowel loops are minimally dilated. However, there is no transition point. There is moderate volume of ascites.

Serum C3 complement levels in ANCA associated vasculitis at diagnosis is a predictor of patient and renal outcome.

To determinate the prognostic significance of low serum C3 at the time of diagnosis of ANCA-associated vasculitis (AAV). Our cohort included 75 consecutive patients with AAV diagnosed from January 2005 to December 2015. C3 levels were measured at the time of diagnosis. Patients were divided into two groups, those with low serum C3 levels (< 0.9g/l) and those with normal serum C3 levels (0.9-1.8g/l). We analysed association between serum C3 levels and both combined and singularly patient and renal survival (ESRD). Small number of relapsed patients did not allow for the statistical analysis to be performed as to weather the low serum C3 is associated with relapse rate in AAV patients. Low serum C3 levels were significantly associated with worse combined end-point patient and renal survival (HR 3.079; 95% CI 1.231-7.701; p = 0.016), and on multivariate adjusted analysis association remained significant (HR 2.831; 95% CI 1.093-7.338; p = 0.032). For both end-points individually low serum C3 levels were significantly associated with poorer patient survival (HR 6.378; 95% CI 2.252-18.065; p < 0.001; on multivariate adjusted analysis HR 4.315 95% CI 1.350-13.799; p = 0.014) and renal survival (HR 3.207; 95% CI 1.040-9.830; p = 0.043; on multivariate adjusted analysis HR 3.679; 95% CI 1.144-11.827; p = 0.029). In our study there was no significant association between serological and patohistological phenotypes and serum C3 levels. Lower serum C3 levels at the diagnosis is associated with poorer patient and renal outcomes in AAV patients.

The potential role of complements in cocaine-induced thrombotic microangiopathy.

Thrombotic microangiopathy (TMA) is a rare disorder characterized by microvascular injury and occlusion resulting in tissue ischemia and dysfunction. TMA occurs in a variety of settings including cocaine use. Although cocaine is widely used in the United States, cocaine-associated TMA is only rarely reported. Therefore, other factors may predispose cocaine users to the development of TMA. Emerging evidence indicates that cocaine activates complements. Therefore, complement activation may contribute to the development of cocaine-induced TMA. Here, we report a cocaine user who presented with renal failure. Renal biopsy demonstrated TMA. Laboratory tests revealed reduced serum complement C3 and normal complement C4 levels indicative of alternative complement activation. We postulate that complement activation is involved in the pathogenesis of cocaine-induced TMA.

Complement factor C4 activation in patients with hereditary angioedema

ObjectivesLow complement factor C4 is usually considered a valuable screening tool for patients with the potentially life-threatening hereditary angioedema with C1-inhibitor (C1-INH) deficiency (C1-INH-HAE). However, there are patients with C1-INH-HAE presenting with normal C4 levels. This means, that C1-INH-HAE may potentially be overlooked, if screening is performed only by measurement of C4. It has been suggested that measurement of C4 activation products is better suited to avoid false negative results. Our aim was to investigate whether total antigenic C4 or non-functional C4c is a better measure of the increased C4 activation in C1-INH-HAE patients. Design and methodsTwo different monoclonal antibodies (mAb) to human C4 were produced: one had specificity for the β-chain of C4 and would thus react with both functional and non-functional C4, and the other was developed against the factor I cleavage site on the α3-domain of C4 and was thus specific for activated, non-functional C4c. With these mAb we investigated plasma from 19 Danish C1-INH-HAE patients in three different enzyme-linked immunosorbent assays (ELISAs): a total antigenic C4 assay, a functional C4 assay and an assay measuring non-functional C4c. ResultsThe amount of total antigenic C4 varied considerably between patients and 2 patients had total antigenic C4 levels in the normal area. Functional C4 was low in all C1-INH-HAE patients. A C4c/C4 ratio showed that around half the C4 measured in patients was non-functional and captured all C1-INH-HAE patients. ConclusionsThis study shows that the C4c/C4 ratio seems to be a better diagnostic measure than total antigenic C4 alone. Our findings underline that screening with total antigenic C4 implies a risk of overlooking C1-INH-HAE patients.

Decreased Serum C3 Levels in Immunoglobulin A (IgA) Nephropathy with Chronic Kidney Disease: A Propensity Score Matching Study.

BackgroundThe effects of low serum C3 levels and the activation of the complement system on the development and the prognosis of IgAN are unclear. The present study aimed to determine whether decreased levels of complement C3 influence the prognosis of IgAN patients with chronic kidney disease.Material/MethodsWe enrolled a total of 1564 patients with primary IgAN diagnosed by renal biopsy at the Chinese PLA General Hospital from January 2011 to March 2015. The endpoint was end-stage renal disease (ESRD) or a doubling of the baseline serum creatinine (D-SCr) level. All patients were using 1: 1 propensity score matching (PSM), and the baseline values were not significantly different between these 2 groups (P>0.05).ResultsDuring a follow-up period, 14 patients in the group with decreased C3 levels reached the endpoint, with 12 patients with normal C3 levels. There was no significant difference between the 2 groups in achieving D-SCr or ESRD (P=0.676). In multivariate Cox analysis, adjusted for demographic and laboratory examination, the risk of reaching the endpoint was comparable in the 2 groups (HR, 0.70; 95% CI, 0.27–1.78; P=0.449;). Furthermore, the risk of reaching ESRD (HR, 0.83; 95% CI, 0.25–2.75; P=0.757) and D-SCr (HR, 1.45; 95% CI, 0.20–10.60; P=0.718) did not differ between the 2 groups.ConclusionsDecreased serum C3 levels in IgA nephropathy with chronic kidney disease did not play a decisive role in renal progression.

DIAGNOSTIC VALUE OF BLOOD NGAL, COMPLEMENT PROTEINS C3 AND C4, IMMUNOGLOBULINS IN CHILDREN WITH HEMOLYTIC-UREMIC SYNDROME

The aim : to determine changes of levels of blood neutrophil gelatinase-associated lipocalin (NGAL), complement proteins C3 and C4, immunoglobulins in children with hemolytic-uremic syndrome (HUS) and to find the relationship between them and factors determining the severity of kidney injury. A prospective study included 159 children: 35 in the acute phase of HUS, 124 – after HUS, at least 6 months after discharge from the hospital and 28 healthy children. NGAL was elevated in all children with HUS more pronounced in those who required renal replacement therapy. Activation of the alternative pathway of the complement system in HUS D «+» due to reduced C3 and normal C4 levels was found. The degree of increasing NGAL and decreasing complement C3 has a close correlation with parameters reflecting the severity of renal damage. At the onset of HUS the decreasing of IgG and IgA with normal IgM levels was found, indicating inadequate humoral protection and the risks of infectious complications.

Analysis of Complete Remission in Systemic Lupus Erythematosus Patients Over a 32‐Year Period

Systemic lupus erythematosus (SLE) is characterized by an unpredictable and fluctuating course. Although various methods have been developed to measure disease activity, there is still a lack of consensus about the optimal criteria for SLE remission. The principal aim of our study was to identify the number of lupus patients achieving a complete remission (implying that for 3 years there were no clinical or serologic features and no treatment with steroids and immunosuppressive drugs) in a single cohort of patients followed for a period of up to 32 years. In addition, we have identified patients in clinical but not serologic remission (known as serologically active, clinically quiescent disease [SACQ]) and vice versa. We were particularly interested to determine the factors associated with complete remission. Eligible patients were followed up in the University College Hospital Lupus cohort from January 1978 until December 2010 for a period of at least 3 years. Complete remission was defined as a period of at least 3 years with clinical inactivity (British Isles Lupus Assessment Group scores of C, D, or E only) and laboratory remission (no antibodies to double-stranded DNA and normal complement C3 levels), and being off-treatment with corticosteroids and immunosuppressants. Antimalarial and nonsteroidal antiinflammatory drugs were allowed. Of 624 lupus patients at our hospital, a total of 532 patients met the strict inclusion criteria for the study. Of these 532 patients, 77 patients (14.5%) achieved complete remission for at least 3 years, and 23 (4.3%) achieved complete remission for a minimum period of 10 years. Ten of these 77 patients were subsequently lost to followup, and, interestingly, flares occurred subsequently in 15 of the 67 remaining patients (22.4%). Three patients relapsed after the tenth year of remission. Forty-five patients (8.5%) fulfilled the requirement for SACQ, and 66 patients (12.4%) achieved only serologic remission. Our study indicated that 14.5% of lupus patients achieved a complete remission for 3 years. However, flares may continue to occur beyond 10 years of remission. Long-term followup of SLE is therefore mandatory.

Tuberculous rheumatism “Poncet's disease”. Case report

Abstract Background Deaths due to tuberculosis have reached 2.5 million cases per year worldwide. Poncet's disease is an infrequent form of tuberculosis characterised by a clinical picture of polyarthritis. Clinical case A 24-year-old male presented with morning stiffness, arthralgias, bilateral symmetric arthritis of the proximal interphalangeal joints, wrists, knees, ankles, and shoulders, and adenomegalies at the cervical, submandibular, left supraclavicular, axillary and inguinal levels, without fever. Laboratory results were as follows: ESR 44 mm/h, C-reactive protein 4.35, normal levels of complement C3 and C4, negative rheumatoid factor and anticyclic citrullinated peptide antibodies, positive antinuclear antibodies with fine speckled pattern (1:320) and cytoplasm (1:160) pattern and negative anti-Smith, -double-stranded DNA, Sjogren's syndrome-antigen A and Sjogren's syndrome-antigen B. Histological report of cervical node tissue revealed granulomatous lesions compatible with tuberculosis. Rheumatoid arthritis and systemic lupus erythematosus were ruled out. Anti-tuberculosis agents were initiated that resolved the clinical picture. Diagnosis of Poncet's disease was confirmed. Conclusion The differential diagnosis between tuberculosis and autoimmune inflammatory joint diseases is a clinical challenge.

Association between anti-Ro 60 kDa (SS-A) autoantibodies and hypocomplementemia in systemic lupus erythematosus patients from Algiers prefectures

BackgroundSystemic lupus erythematosus (SLE) is characterized by a vicious cycle maintaining systemic inflammation. It starts by autoantibody production, immune complex formation and complement activation that contribute to inflammation, tissue damage and further autoantibody production. Aim of the workTo evaluate the association between the auto-antibodies (abs), circulating immune complexes (CIC), and complement activity in SLE patients. Patients and methodsThis study involved 30 female SLE patients analyzed for autoantibodies, complement profile including complement hemolytic 50 (CH50), alternative pathway 50, factor B, C1q, C2, C3 and C4 as well as C1q-CIC. SLE disease activity was assessed by the SLE Disease Activity Index (SLEDAI). ResultsThe age of patients was 34±12.8years, disease duration was 5.2±3.2years and their mean SLEDAI was 9.96±4.2. Anti-SSA, anti-dsDNA, anti-C1q abs, and CIC were detected in 36.7%, 50%, 50% and 30% of patients, respectively. Anti-SSA were higher in patients with lower compared to normal CH50 activity and C3 level (24.7 vs 88.6U/ml; p=0.002 and 118.6±25.18U/ml vs 15.9±7.3; p<0.0001 respectively) than the other autoantibodies. Increased CIC were higher in patients with lupus nephritis and were associated with anti-SSA, anti-SSB, anti-C1q, anti-Sm and in patients with low CH50 activity. The CIC significantly correlated with anti-C1q (r=0.69, p<0.0001), anti-SSA (r=0.5, p=0.005) and negatively with CH50 (r=−0.4, p=0.046). ConclusionsThe current study confirms that the etiopathogenic anti-SSA autoantibodies are the most associated with hypocomplementemia in SLE. This would stimulate future researches for validation of predictive biomarkers earlier than hypocomplementemia which is still the major unmet need in lupus research and patient care.