Antineutrophil Cytoplasmic Antibody Levels Research Articles

Comparison of different ANCA detection methods in a predominantly MPO-ANCA-associated vasculitis cohort

We compared different antineutrophil cytoplasmic antibody (ANCA) detection methods using a predominantly myeloperoxidase (MPO)-ANCA-associated vasculitis cohort. Stored sera from 147 patients with untreated ANCA-associated vasculitis (AAV), including microscopic polyangiitis and granulomatosis with polyangiitis (n = 115 and 32, respectively), and 124 disease controls were tested for P-ANCA and C-ANCA with immunofluorescence (IIF), and for MPO-ANCA and proteinase 3 (PR3)-ANCA with different antigen-specific immunoassays: direct enzyme-linked immunosorbent assay (ELISA), chemiluminescent enzyme immunoassay (CLEIA), third-generation fluorescent enzyme immunoassay (FEIA), and latex turbidimetrical immunoassay (LTIA). In addition, MPO-ANCA and PR3-ANCA titers were calibrated using certified reference materials (CRMs). The sensitivities and specificities for AAV diagnoses were 95% and 94% (IIF), 86% and 98% (ELISA), 93% and 94% (CLEIA), 92% and 96% (FEIA), and 68% and 88% (LTIA). Dual IIF/antigen-specific immunoassay testing reduced diagnostic accuracies from 94% to 93%. The quantitative agreement between ANCA levels measured using CLEIA and FEIA and calibrated using CRMs was not good. In conclusion, this study demonstrated the high performance of antigen-specific immunoassays for AAV diagnosis in a predominantly MPO-ANCA-associated vasculitis cohort and suggested that the benefit of dual IIF/antigen-specific immunoassay testing is limited. Standardizing ANCA measurements using different immunoassays was difficult, even when using CRMs.

Clinical Significance of Overlap Syndrome of Histologically Confirmed Lupus Nephritis with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

Objectives: We applied the 2022 American College of Rheumatology/ European Alliance of Association for Rheumatology (ACR/EULAR) criteria for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) to patients histologically diagnosed with lupus nephritis (LN) to investigate the overall rate of and initial contributing factors to the reclassification of overlap syndrome of LN with AAV (OS-LN-AAV). Methods: We retrospectively reviewed the medical records of 1292 patients with systemic lupus erythematosus (SLE) and included 164 patients with LN in this study. Patient demographics, SLE manifestations, LN classes, and laboratory data, including ANCA levels, were recorded. All-cause mortality and end-stage kidney disease (ESKD) were evaluated as poor outcomes. Results: The median age of the 164 patients was 37.0 years, and 12.2% were men. The overall reclassification rate was 37.8%, of which 34.1% and 3.7% of the patients were reclassified as having OS-LN-microscopic polyangiitis and OS-LN-granulomatosis with polyangiitis (GPA), respectively, but none as having eosinophilic GPA. ANCA positivity and AAV-suggesting lung lesions were major contributors to OS-LN-AAV reclassification. When patients were compared based on OS-LN AAV reclassification, ANCA positivity and myeloperoxidase-ANCA (or P-ANCA) positivity favoured for OS-LN-AAV reclassification, whereas oral ulcers did not. However, OS-LN-AAV reclassification did not affect all-cause mortality or ESKD. Conclusions: This is the first study demonstrating a 37.8% reclassification rate in patients histologically diagnosed with LN using the 2022 ACR/EULAR criteria for AAV. Furthermore, it was also the first to reveal ANCA positivity and AAV-suggesting lung lesions as major contributors to OS-LN-AAV reclassification.

Dynamically changing antineutrophil cytoplasmic antibodies in granulomatosis with polyangiitis: A case report

BACKGROUND Granulomatosis with polyangiitis (GPA) is one of the most prevalent forms of the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. GPA is characterized histologically by necrotizing granulomatous inflammation in addition to vasculitis. The diagnosis of GPA depends on clinical presentation, serological evidence of a positive ANCA, and/or histological evidence of necrotizing vasculitis or granulomatous destructive parenchymal inflammation. Cytoplasmic ANCA (c-ANCA) is positive in 65%-75% of GPA patients, accompanied by proteinase 3 (PR3), the main target antigen of c-ANCA, another 5% of GPA patients had negative ANCA. CASE SUMMARY The patient, a 52-year-old male, presented with unexplained nasal congestion, tinnitus, and hearing loss. After a duration of 4 months experiencing these symptoms, the patient subsequently developed fever and headache. The imaging examination revealed the presence of bilateral auricular mastoiditis and partial paranasal sinusitis, and the ANCA results were negative. The anti-infective therapy proved to be ineffective, but the patient's symptoms and fever were quickly relieved after 1 wk of treatment with methylprednisolone 40 mg once a day. However, after continuous use of methylprednisolone tablets for 3 months, the patient experienced a recurrence of fever accompanied by right-sided migraine, positive c-ANCA and PR3, and increased total protein in cerebrospinal fluid. The patient was diagnosed with GPA. After receiving a treatment regimen of intravenous methylprednisolone 40 mg/d and cyclophosphamide 0.8 g monthly, the patient experienced alleviation of fever and headache. Additionally, the ANCA levels became negative and there has been no recurrence. CONCLUSION For GPA patients with negative ANCA, there is a potential for early missed diagnosis. The integration of histopathological results and multidisciplinary communication plays a crucial role in facilitating ANCA-negative GPA.

On the problem of differential diagnosis in the detection of antineutrophil cytoplasmic antibodies

Vasculitides associated with antineutrophil cytoplasmic antibodies (ANCA) are a group of systemic autoimmune diseases characterized by necrotizing lesions of the walls of predominantly small vessels and the presence of ANCA against proteinase 3 or myeloperoxidase. However, an increase in ANCA levels can also be observed in other diseases, including autoimmune, malignant and infectious diseases, which complicates the interpretation of clinical and laboratory data and requires a differential diagnosis.

Glomerulonephritis as a renal manifestation in a patient with systemic sclerosis overlapped with anti-neutrophil cytoplasmic antibody-associated vasculitis

Introduction and Importance: Systemic sclerosis (SSc) is a systemic immune disorder that may overlap with other rheumatologic disease; however, overlapping with antineutrophil cytoplasmic antibody-associated vasculitis is rare. Case Presentation: A 28-year-old Syrian male patient with SSc diagnosed according to the American College of Rheumatology/European League against Rheumatism 2013 criteria with a disease duration of 4 years, was admitted to the hospital complaining of palpable purpura in the lower limbs and hemoptysis and later, a rise in creatinine level. Laboratory tests showed high levels of perinuclear antineutrophil cytoplasmic antibodies (p-ANCA). The renal biopsy results were consistent with the diagnosis of glomerulonephritis. He was treated with methylprednisolone, cyclophosphamide, and rituximab, as he was diagnosed with SSc overlapping antineutrophil cytoplasmic antibody-associated vasculitis. Clinical Discussion: SSc most commonly renal manifestations are proliferative vasculopathy leading to scleroderma renal crisis. However, other types of renal involvement were also reported in SSc patients with comorbid autoimmune diseases such as glomerulonephritis and signs of concurrent vasculitis. SSc may overlap with rheumatoid arthritis, systemic lupus erythromatosus, polymyositis/dermatomyositis (PM/DM), and Sjogren Syndrome. Overlapping with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is mentioned in rare cases. The authors reported a rare case of overlapping SSc with antineutrophil cytoplasmic antibody-associated vasculitis with renal involvement. Conclusion: The authors revealed a rare case of overlapping SSc with antineutrophil cytoplasmic antibody-associated vasculitis with renal involvement. In SSc, renal involvement as glomerulonephritis is infrequent and should be detect in other rheumatologic disease such as systemic lupus erythematosus or antineutrophil cytoplasmic antibody-associated vasculitis.

Ulnar Nerve Palsy as the Initial Presentation of Small Vessel Vasculitis With a Negative Antineutrophil Cytoplasmic Antibody Level

Small-vessel vasculitis is a rare disease entity that affects the arteries, arterioles, capillaries, and venules of the circulatory system. Small vessel vasculitis can cause severe small vessel inflammation and multisystem involvement. The respiratory tract and kidneys are the most commonly affected organs, and occasionally neurological manifestations can occur. But neurological manifestation as the initial presentation without other system involvement is very rare. We report a case of a 16-year-old previously well female patient presenting with right lower limb distal muscle weakness associated with malaise, lethargy, and multiple joint pains for 2 weeks. On examination, she had palpable purpura below the knees with right sided ulnar nerve palsy. Her antineutrophil cytoplasmic antibody and antinuclear antibody testing was negative. A skin biopsy showed vasculitis involving small vessels. She was started on Prednisolone 60mg daily, followed by Mycophenolate Mofetil 500mg twice daily, and physiotherapy. She had a good clinical response to treatment over time.

The intrinsic coagulation pathway plays a dominant role in driving hypercoagulability in ANCA-associated vasculitis

AbstractThe risk of a venous thrombotic event (VTE) is increased in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV); however, a detailed understanding of the underlying mechanisms of hypercoagulability is limited. We assessed prospectively different coagulation parameters in 71 patients with active AAV at baseline and after 6 months of follow-up. D-dimers and fibrinogen were increased in most patients at presentation and remained elevated in half of the patients. Particularly, thrombin-antithrombin (T:AT) complex and activated coagulation factors in complex with their natural inhibitors of the intrinsic coagulation pathway (ie, activated FXII:C1 esterase inhibitor [FXIIa:C1Inh], FXIa:AT, and FXIa:alpha1-antitrypsin [FXIa:α1AT]) were profoundly elevated in patients at baseline. Thrombin formation was dominantly correlated with coagulation factors of the intrinsic pathway (ie, FXIIa:AT, FXIa:AT, FXIa:α1AT, and FXIa:C1Inh) compared to the extrinsic pathway (ie, FVIIa:AT). Hypercoagulability correlated with higher disease activity, ANCA levels, C-reactive protein, serum creatinine, and proteinuria. VTEs were observed in 5 out of 71 (7%) patients within 1 month (interquartile range, 1-5) after inclusion. Baseline T:AT levels were significantly higher in patients with VTE than in those without VTE (P = .044), but other clinical or laboratory markers were comparable between both groups. Hypercoagulability is dominantly characterized by activation of the intrinsic coagulation pathway and elevated D-dimers in active AAV. The driving factors of hypercoagulability are yet to be studied but are most likely related to an interplay of increased disease activity, vascular inflammation, and endothelial damage. Future targets for intervention could include inhibitors of the intrinsic coagulation pathway and compounds specifically reducing the hyperinflammatory state.

Solo Addition of Mepolizumab Turned Antineutrophil Cytoplasmic Antibody Negative and Achieved Glucocorticoid Discontinuation in a Patient with Eosinophilic Granulomatosis with Polyangiitis: A Case Report.

The IL-5 inhibitor mepolizumab is beneficial in eosinophilic granulomatosis with polyangiitis (EGPA), and the inhibition of antineutrophil cytoplasmic antibody (ANCA) production has been suggested as a possible mechanism. We herein report a 78-year-old Japanese man with EGPA who received solo mepolizumab 300 mg twice for elevated ANCA levels, which led to subsequent GC discontinuation after achieving remission. The patient was able to be freed from the adverse events associated with long-term GC treatment, and the sole addition of mepolizumab also proved that mildly elevated ANCA could be converted to a negative result, thus leading to GC discontinuation.

Maintenance of remission of ANCA vasculitis by rituximab based on B cell repopulation versus serological flare: a randomised trial

ObjectiveTo compare two long-term remission maintenance strategies for antineutrophil cytoplasmic antibody (ANCA) vasculitis.MethodsWe conducted a prospective, single-centre, open-label, randomised controlled trial of patients with ANCA vasculitis in remission after completing...

Clinical significance of serum levels of Saccharomyces cerevisiae IgA, IgG and perinuclear antineutrophil cytoplasmic antibodies in the differential diagnosis of inflammatory bowel diseases

Clinical significance of serum levels of Saccharomyces cerevisiae IgA, IgG and perinuclear antineutrophil cytoplasmic antibodies in the differential diagnosis of inflammatory bowel diseases

Clinical efficacy of protein A immunoadsorption therapy on severe ANCA-associated vasculitis renal injury.

The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of diseases involving multiple systems, and kidney is one of the most commonly involved target organs. Some patients may rapidly progress to end-stage renal disease in a short time. Whereas some patients have poor remission and renal prognosis after standard induction therapy. As a selective blood purification therapy, protein a immunoadsorption (PAIA) has shown great advantages on treating of severe autoimmune diseases. This study aims to evaluate the short-term efficacy of PAIA therapy combined with glucocorticoids and immunosuppressants on treating of severe AAV renal injury. A total of 10 AAV cases with severe kidney involvement in the Second Xiangya Hospital of Central South University from 2019 to 2020 were selected for this retrospective study. During the induction remission stage, each patient was treated with PAIA on the basis of standard therapy of glucocorticoids and immunosuppressive treatment. Before and after the initial treatment, 1 month and 3 months after treatment, clinical data including demographic characteristics, immunological indicators, and Birmingham Vasculitis Activity Score (BVAS) were compared. The related adverse reactions during treatment were recorded to evaluate the short-term efficacy. In this study, all 10 patients were MPO positive, and 2 patients were PR3 positive (≥2.3 U/mL). There are 6 males and 4 females at (61.5±11.4) years old, with the median time from onset to admission to hospital at (2.8±1.8) months. Multisystem damage, especially kidney damage, can be seen with eGFR lower than 30 mL/(min·1.73 m2). During the 3-month follow-up, BVAS, erythrocyte sedimentation rate, and hemoglobin of 10 patients showed continuous improvement compared with the initial admission levels (all P<0.05). ANCA titer, serum creatinine and urine red blood cell were all decreased and eGFR levels were increased in 3 months after treatment (all P<0.05). Serum albumin, urinary protein, C-reactive protein and complement levels showed no significant changes after treatment (all P>0.05). One patient who had received renal replacement therapy was still dialysis dependent after PAIA treatment. One patient who had transient hypotension was corrected by routine treatment. The rest of the patients were all tolerant with PAIA during their treatments. Treatment with PAIA combined with glucocorticoids and cyclophosphamide can rapidly lower serum ANCA level and improve disease activity in patients with AAV complicated with severe kidney damage, suggesting a good short-term renal prognosis and good overall safety.

#4790 SERUM BIOMARKERS AS PREDICTORS OF RENAL DAMAGE IN ANCA-ASSOCIATED VASCULITIDES

Abstract Background and aims Despite therapeutic advances, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) carry poor renal and survival outcomes. Prognostic elements are needed to guide treatment. Several studies explored determinants of AAV outcomes, but predictive factors are not well established. Poor prognosis factors have been lower glomerular filtration rate, lower serum C3, C3 deposition on immunofluorescence (IF), and recently platelet count below 250 × 109/L. Histopathological lesions have also been related to renal outcomes. In this study we aim to correlate serum immune and inflammatory biomarkers with renal histological lesions’ severity. Methods We retrospectively analysed histopathological findings of adults with biopsy-proven AAV renal involvement through Berden's histopathological classification (BHC) classes, Brix's renal risk score (BRS), interstitial fibrosis and tubular atrophy (IFTA) and crescentic glomeruli percentages (%), C3 positive IF and presence of interstitial hemorrhage (IH). Patients’ ANCA titer (ANCAd) measured by ELISA, serum C3 and C-reactive protein (CRP) were documented at diagnosis. ANCA titer was also registered at last follow-up date (ANCAf). Univariate statistical analysis was used to correlate every biomarker with every histologic variable mentioned. C3 and CRP were used as continuous variables and ANCA titers as continuous and categorical variables. As a continuous variable, ANCA titers above laboratorial detection were not considered (i.e. &amp;gt;134). Seronegative AAV were not considered for titer analysis. BRS was considered as continuous variable for its score and as categorical for its risk group. Multivariate analysis was used to identify independent predictors renal biopsy findings. Results We included 46 patients with biopsy-proven AAV kidney involvement from January 2006 to January 2023, 65.2% male (n = 30), median age 66.5 (60.75-74.5), 78.3% (36) MPO, 15.2% (7) PR3 and 6.5% (3) seronegative; and 6.5% (3) had concomitant anti-GBM+ (all MPO). Categorization by ANCAd revealed 7.7% (3) 0-19 UI/mL, 7.7% (3) 20-39, 7.7% (3) 40-59, 20.5% (8) 60-99, 12.8% (5) 100-134 and 43.6% &amp;gt;134. According to BHC, biopsies were: 17.4% (8) global sclerotic, 28.3% (13) mixed, 39.1% (18) crescentic, and 15.2% (7) focal. According to BRS, 2.2% (1) had low risk, 28.3% (13) medium risk and 58.7% (27) high risk of ESKD. 5 biopsies had incomplete information for a score result. Median BRS was 9 – high risk. IF C3 was positive 28.3% (16) biopsies, and IH in 10.9% (5). Median % IFTA was 40% and median %crescentic was 33%. In univariate analysis, ANCAd did not correlate to BHC class both as continuous and categorical variable (p = 0.477 and p = 0.685 respectively), nor to %IFTA (p = 0.935, p = 0.938), nor %crescents (p = 0.975, p = 0.938), nor C3 IF staining (p = 0.690, p = 0.344), nor IH presence (p = 0.773, p = 0.897), nor to BRS risk groups (p = 0.339, p = 0.584). ANCAd titer did not correlate to BRS score value (p = 0.072, r = 0.372), both as continous variables. However, ANCAf did correlate to BRS´s risk groups (p = 0.037), with ANCAf values higher in the high-risk compared to the medium-risk group (p = 0.016). In multivariate analysis including age and gender, ANCAf persists as a predictor of BRS´s risk groups (p&amp;lt;0.001, model p&amp;lt;0.001). C3 levels at diagnosis did not have statistically significant correlation with neither histological finding: BHC class (p = 0.282), BRS score (p = 0.683), % IFTA (p = 0.753), % crescents (p = 0.989), C3 on IF (p = 0.472) and IH (p = 0.773). No significant correlation was seen when considering CRP at diagnosis: BHC class (p = 0.162), BRS (p = 0.276), %IFTA (p = 0.343), %crescents (p = 0.071), C3 on IF (p = 0.657) and IH (p = 0.951). Conclusions ANCA titer at diagnosis, serum C3 and CRP did not correlate with histological severity and chronicity lesions in our population. Nonetheless, larger cohorts, systematization of biopsy findings and studies on newer biomarkers might bring helpful information to expected prognosis and initial therapeutic approaches. A positive correlation between ANCA levels at the last follow-up date and medium and high-risk BRS groups on initial biopsy might be further explored in larger studies.

#5555 TAKAYASU ARTERITIS IN THE TIME OF SARS-COV-2

Abstract Background and Aims SARS CoV 2 infection is characterized by pulmonary, cardiovascular, neurological and other complications. New onset hypertension after SARS Cov 2 infection was observed in various studies with an unclear mechanism. Vessel inflammation is a common finding in these patients. Case A young woman (24 years old) referred to our Unit for high blood pressure levels appeared few days after SARS COVID 2 infection. She had a positive familiar history of hypertension. A 24 hours blood pressure monitoring confirmed hypertension and the patient was treated with a beta-blocker and referred to the nephrologist. Physical examination was negative and peripheral pulses were palpable. Blood pressure was 150/90 mmHg without significative discrepancy (&amp;lt;10 mmHg) between right and left arm and between upper and lower limbs. Carotid-femoral and carotid-radial pulse wave velocity was in the upper limit of the normal range (9.8 and 8.0 m/sec respectively), renal function was preserved (serum creatinine 0.6 mg/dl, eGFR 154 ml/min) and proteinuria was 450 mg/die. C-reactive protein was 13 mg/L. Complement components C3 and C4 as well as IgG and anti-neutrophil cytoplasmic antibody (ANCA) levels were in the normal range. IgA and IgM were slightly elevated and anti-nuclear antibody (ANA) levels were 1:160. TSH was in the normal range. Patient was switched to calcium channel blockers and a screening to exclude secondary hypertension was performed. Hormonal profile showed hypersecretion of cortex and medullary adrenal gland (high renin and aldosterone, plasma and urinary cortisol, and epinephrine levels). Patient was treated with ACE inhibitor and showed an optimal blood pressure profile. Abdominal-Chest CT angiography detected no increase in adrenal gland dimension. Conversely, a left renal artery stenosis and a mild enlargement of the para-aortic tissue, suggestive of a retroperitoneal fibrosis, was described (Figure 1). A Doppler ultrasound examination confirmed a high systolic peak velocity in left renal artery and a low resistive index in the left kidney. According to the diagnosis of renal fibrosis, patient was treated with oral prednisone at a dosage of 1 mg/Kg/BW. Three months later, Doppler ultrasound and CT were materially unchanged. After a case revision and a negative evidence of inflammation at PET-FDG examination, the Takayasu Arteritis diagnosis was formulated and the patient underwent left renal artery angioplasty. Oral prednisone was tapered and methotrexate was started. One month later blood pressure and Doppler ultrasound velocimetric parameters were normalized. Conclusion This case report suggests that Takayasu arteritis may occur after SARS COVID 2 infection.

Anti-neutrophil cytoplasmic antibody associated vasculitis following rituximab: Outcomes of 50 patients in a tertiary single centre

Introduction: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an uncommon condition with heterogeneous multisystem organ involvement and significant morbidity and mortality. This study aimed to characterize the clinical features and laboratory characteristics, including B cell depletion, the ability to reduce corticosteroid dosage, and outcomes, of patients with AAV following rituximab treatment. Methods: Retrospective clinical and laboratory data were collected from patients with AAV who visited our lupus unit, including 50 treated with rituximab. Numeric response variables (median and range) were collected, including age, follow-up duration, disease duration, and Birmingham Vasculitis Activity Score (version 3). Statistical analyses were conducted using the SPSS 25.0 software. Statistical significance was considered a p-value &lt;.05. Results: Of the 50 patients, 40 (80%) had granulomatosis with polyangiitis, 30 (75%) achieved remission, and 10 (25%) had active disease. Fifteen patients (30%) had positive ANCA levels at their last ANCA level assessment follow-up. Thirty-seven patients (74%) had B cell depletion, and 30 (81.1%) were in remission. Their median immunoglobulin levels were 7.6 (2.7–21.2) g/L for IgG, 0.5 (0.07–1.71) g/L for IgM, and 1.83 (0.14–4.87) g/L for IgA. Forty-two patients (84%) were able to lower their steroid dose to &lt;7.5 mg, with 36 (85.7%) in remission and six (14.3%) having active disease ( p = .003). Conclusion: Our data suggests that most patients experience clinical remission after rituximab maintenance treatment. Half the patients were in remission, with normal creatinine levels and inflammatory markers. In addition, our patients could reduce steroid use.

Wegener’s Granulomatosis Revealed by Bilateral Orbital Inflammatory Pseudotumor: a Case Report and Literature Review

Purpose: To describe the chronology and the extent of orbital involvement in a case of granulomatosis with polyangiitis (GPA). Methods: Descriptive case report and literature review. Results: A thirty-two years old male consulted with the following complaints: A retro-orbital discomfort in both eyes, a bilateral fast progressive proptosis and a decrease in visual acuity in the left eye. Eye examination revealed a proptosis, ptosis, epiphora and a motility restriction and peripheral corneal ulcer infiltrates with nodular scleritis in the left eye. A palpable orbital mass was located in the sub temporal orbit in both eyes. Orbit magnetic resonance imaging (MRI) unveiled a diffuse and elongated enlargement of both lacrimal glands with enhancing mass in the superior lateral aspect of both eyes globe. The diagnosis of an orbital pseudotumor was suspected. The biological work-up revealed a high blood levels of inflammation markers and antineutrophil cytoplasmic antibodies (c-ANCA). The diagnostic of active systemic granulomatosis with polyangiitis was then made. Conclusion: As seen in this case, clinicians should consider a differential diagnosis of granulomatosis with polyangiitis in patients with an orbital pseudotumor mimic aspect.

The effect of various forms of treatment of vasculitis on C3, C4 and C5a complement levels in infants and children attending Assiut University Children Hospital (AUCH)

Vasculitis is an umbrella term for various and heterogeneous disorders sharing the presence of inflammation of blood vessel walls (Geetha &amp; Jefferson, 2020). Immune cell infiltrates involve the presence of leukocytes in the vessel with immune-complex deposition, which implies the activation of the complement system and then the swelling and destruction of vessel mural structures. The lumen is narrowed or occluded leading to ischemia and necrosis (Chimenti et al., 2015). It produces local symptoms resulting in hypoperfusion, infarction and hemorrhage and systemic symptoms with an increase in acute phase reactants (Salvador, 2020). According to the size of the blood vessel affected and the distribution of vascular injury, pediatric vasculitis is classified into small vessel vasculitis as in Henochonlein Purpura (HSP), medium-sized vessel vasculitis as in Kawasaki disease and large vessel vasculitides affecting the aorta and its proximal branches. Some forms of small vessel vasculitis are characterized by the presence of antineutrophil cytoplasmic antibodies (ANCAs), whereas others are associated with immune complex deposition in affected tissues. Clinical presentation supported by specific laboratory test, imaging, and confirmatory histology are necessary in order to perform vasculitides’ diagnosis (Sivaraman et al., 2020). To assess the severity of vasculitis and response to treatment, urinary biomarkers such as albumin/creatinine ratio (A/C ratio) in urine have been proved to be easily done and correlated well with both clinical and serological results (Zhang, 2020). Aim of Work: The aim of this study is to assess the effect of various forms of drugs, used in treatment of vasculitis, on the serum levels of complements (C3, C4, and C5a) and Antineutrophil cytoplasmic antibodies (ANCA), in infants and children attending Assiut University Children Hospital (AUCH). Conclusion: In conclusion, cases on combined Methotrexate and Steroid therapy scored best regarding the lowering of C5a level in serum, however, in our cases as a whole, the level of C5a didn’t differ significantly from its level in control. Although the 3 arms of therapy used in this study had good effect on C3 &amp; C4 levels, yet their effect on C5a level was not significant from control. This finding could be explained by the fact that most of our studied cases were of the immune-complex deposition diseases type (which have no effect on C5a) and were ANCA negative. Therefore, C5a inhibitor drugs probably will not be suitable in treatment of most common causes of pediatric vasculitis encountered in this series. Perhaps, this type of therapy might be used in ANCA-Positive associated vasculitides, e.g. Wegener’s Granulomatosis. Further research with bigger number of ANCA positive cases is needed to decide whether such cases could benefit from the use of C5a inhibitors or not.

The role of a conjunctival biopsy in the diagnosis of eosinophilic granulomatosis with polyangiitis with ocular involvement

A 33-year-old Asian man presented with redness, swelling, and blurring of vision in both eyes for 1 month associated with headache and pain. The patient had a history of allergic rhinitis with a progressive hearing loss for 3 months, followed by bell's palsy. Given his elevated serum cytoplasmic anti-neutrophil cytoplasmic antibody (C-ANCA) and erythrocyte sedimentation rate (ESR) levels as well as computed tomography head, orbit, and peripheral nervous system that showed marked bilateral mastoiditis with opacification of the right middle ear canal and enlargement of the bilateral lacrimal gland, the suspicion of small vessel vasculitis with ocular and ear involvement was high. Because there was no significant lung or kidney involvement, a conjunctival biopsy was attempted, which revealed small capillaries surrounded by eosinophils and plasma cells. Because there are no validated diagnostic tests for eosinophilic granulomatosis with polyangiitis (EGPA), a conjunctival biopsy can be valuable and minimally invasive in the early diagnosis and treatment of small vessel vasculitis.

Clinical Significance of Antineutrophil Cytoplasmic Antibody Positivity in Patients Infected with SARS-CoV-2.

Objectives: To investigate the rate of antineutrophil cytoplasmic antibody (ANCA) positivity and its clinical significance in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: This study included 178 patients infected with SARS-CoV-2 who were enrolled in a cohort at a single centre. Myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA levels in stored blood sera were measured using immunoassay kits. Mortality, mechanical ventilator care, and severe infection were assessed as three poor outcomes. The 2022 American College of Rheumatology and the European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria for the three subtypes of AAV were applied only to patients who had MPO-ANCA or PR3-ANCA among study subjects. Results: The detection rate of ANCA positivity was 18.5%. MPO-ANCA and PR3-ANCA were found in 22 (12.4%) and 14 (7.9%) patients, respectively. However, neither MPO-ANCA nor PR3-ANCA affected the three poor outcomes. According to the new criteria, 12 (6.7%) and 21 (11.8%) patients were classified as having granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), respectively. Conclusions: SARS-CoV-2 infection may increase the rate of ANCA positivity. Although it might not affect poor outcomes, it might contribute to the classification of GPA and MPA despite uncertain clinical significance.

Infective endocarditis misdiagnosed as cANCA – associated vasculitis

A previously healthy 37-year-old man was admitted to a nephrology clinic due to the left-sided abdominal pain, petechiae and recurring hematuria. Laboratory tests revealed high levels of C-reactive protein and Antineutrophil Cytoplasmic Antibodies (cANCA). On this basis, vasculitis was suspected and prednisone in high doses was administered. After 30 days of immunosuppressive treatment, due to persistence of symptoms, the patient was referred for an ambulatory echocardiographic study, and because of the abnormal result, he was admitted to our department. On admission, the patient was clinically in good condition. However, the physical examination revealed a systolic-diastolic heart murmur. Transthoracic echocardiography demonstrated a vegetation attached to the non-coronary aortic leaflet and severe aortic insufficiency. Additionally, an abnormal, perforated, bulging of the anterior mitral leaflet was present, with severe mitral insufficiency (Figure 1). Three blood cultures were positive for Streptoccocus sanguinis. Therefore, the patient was diagnosed with IE according to the modified Duke criteria. Subsequently, the treatment was adjusted to include intravenous antibiotic therapy with vancomycin and ceftriaxone. Afterwards, the patient was qualified for the replacement of the aortic and mitral valves with mechanical valve prostheses. The procedure was uneventful and the patient was discharged home in good condition. The medical history of this patients is an outstanding example of how complex and misleading the IE diagnosis can be. A selected laboratory test, like cANCA is indeed an important diagnostic marker for vasculitis [1,2]. However, several infectious diseases have been reported to stimulate positive cANCA tests and therefore to mimic vasculitis. One of them is infective endocarditis, which is known to initiate the immune complex disease in about 25% of patients [3,4]. One could speculate that an immunosuppressive treatment, in our patient might have led to a blunted antibacterial response, and potentially to the expansion of the endocardial infection with the bivalvular involvement, while reducing clinical symptoms. Our patient can be a reminder of the clinical rule, that before the definitive diagnosis and treatment of suspected vasculitis, an active infection, especially IE must be excluded [5].

Studying of Some Immunological Parameters in Patients with Inflammatory Bowel Disease ( IBD ) in Al-Anbar Province

The serum levels of interlukine-17A and interlukine-17F were determined using ELISA technique for quantitative determination of IL-17A and IL-17F concentrations in serum. A comparison in Immunological parameters between the two groups (patients and control) showed that there was a significant difference in levels of IL-17 A and IL-17F with p-value (<0.05). The means were: IL-17 A (79.29 pgml),( 18.72 pgml ) and IL-17F(226.4 pgml ),( 29.09 pgml ) respectively. Also the serum levels of p ANCA and c ANCA were determined using Enzyme-linked immunosorbent assay ELISA technique for quantitative determination of pANCA and c ANCA concentrations in human serum. There was a significant difference in levels of perinuclear antineutrophil cytoplasmic antibodies (pANCA) and cytoplasmic antineutrophil cytoplasmic antibodies(c ANCA ) with p-value(<0.05), the means were: pANCA ( 60.93 ngml), (10.31ngml), and c ANCA (35.78 ngml), (8.341ngml) respectively.