Immunoglobulin A Vasculitis Patients Research Articles

Can the affected intestinal segment visualized on abdominal ultrasound predict gastrointestinal tract bleeding in immunoglobulin A vasculitis?

To evaluate immunoglobulin A vasculitis (IgAV) patients with gastrointestinal (GI) tract involvement and to reveal the relationship between the location and extent of the affected intestinal segment detected on the initial abdominal ultrasound (US) and GI tract bleeding. This medical record review study was conducted on 117 IgAV patients with GI tract involvement between January 2016- June 2023. Patients were divided into two groups as those with (n=28) and without (n=89) GI tract bleeding. Predictors of GI tract bleeding were investigated by comparing demographic, clinical characteristics and laboratory findings. Gender, age at diagnosis, symptoms at admission, rash distribution, GI tract complaints, and the elapsed time until the development of GI tract symptoms were similar in both groups. There was no difference between small intestinal, large intestinal or small+large intestinal involvement (p=0.89). The ileum was the most commonly affected intestinal segment in patients with and without GI tract bleeding (p=0.37). Jejunal wall thickening (p=0.04) and the number of affected intestinal segments (p=0.008) were higher in patients with GI tract bleeding. In IgAV patients, jejunum involvement and affected multiple intestinal segments shown by abdominal US are associated with GI tract bleeding.

A case of de novo glomerulonephritis following COVID-19 in a patient with preexistent IgA vasculitis.

During the unprecedented COVID-19 outbreak, new-onset or relapsing glomerulonephritis, such as ANCA-associated glomerulonephritis and Immunoglobulin A (IgA) nephropathy, following COVID-19 has been reported. However, to date, the association of COVID-19 with preexistent IgA vasculitis (IgAV) remains unclear. Here, we present the case of a 20-something old Japanese woman with preexistent IgAV who newly developed glomerulonephritis following COVID-19. At the diagnosis of IgAV, she had cutaneous purpura, joint pains, and gastrointestinal symptoms, but no signs of kidney involvement. Three months ago, she was tested positive for COVID-19 and subsequently developed hematuria and proteinuria. She was then admitted to our hospital and renal biopsy showed glomerular mesangial expansion and hypercellularity and cellular and fibrocellular crescents, accompanied by diffuse IgA and C3 deposits. With the diagnosis of de novo IgAV nephritis, the patient was treated with intravenous methylprednisolone followed by oral prednisolone. She had favorable responses to this treatment and has achieved and maintained the remission of hematuria and proteinuria after initiation of glucocorticoid therapy. Our case highlights that immune response to SARS-CoV-2 infection could trigger the onset of glomerulonephritis in the IgAV patients who have no renal involvement.

Assessment of Oxidative Stress and Plasma Gelsolin Levels in Children with IgA Vasculitis

Oxidative stress has been proposed to contribute to the pathogenesis of immunoglobulin A vasculitis (IgAV), but the available data remain insufficient. Our goal was to determine the role of the oxidant-antioxidant system and plasma gelsolin (pGSN) in patients with IgAV and its relationship with organ involvement. In the study, 30 individuals with IgAV diagnoses and 30 healthy controls were enrolled. All patients were examined in both the active and remission periods. Serum malondialdehyde (MDA), superoxide dismutase (SOD), and pGSN levels were measured. Compared with the remission and control groups, active IgAV patients had higher serum MDA levels; however, this difference was not statistically significant. When comparing the acute period to remission and control, serum SOD levels were somewhat lower; however, the difference was not statistically significant (>0.05). pGSN levels were prominently low in IgAV patients both in the acute and remission phases (<0.05). No correlation was found between organ involvement, serum MDA, antioxidant enzyme (SOD), and pGSN levels. Low pGSN levels in patients with IgAV may be due to pGSN consumption during the acute episode of the inflammatory process. This may tilt the delicate equilibrium between oxidants and antioxidants, potentially amplifying reactive oxygen species generation.

Clinical characteristics and risk factors of cardiac involvement in pediatric immunoglobulin A vasculitis: A 7-year retrospective study from a single tertiary medical center.

Immunoglobulin A vasculitis(IgAV) is the most common form of systemic vasculitis affecting children. To date, cardiac involvement in pediatric IgAV has not been fully investigated and its prevalence may be underestimated. This study aims to reveal the clinical and laboratory characteristics of cardiac involvement in pediatric IgAV and further determine its risk factors. A total of 1451 children with IgAV were recruited between January 2016 and December 2022. According to the severity of cardiac involvement, the patients were divided into the myocarditis/suspected myocarditis group, cardiac abnormalities group, and non-cardiac involvement group. Demographic, clinical, and laboratory characteristics were retrospectively extracted from the individual data collected in the medical records. Among the 1451 pediatric IgAV patients, 179 (12.3%) were identified with cardiac involvement, including 154 (10.6%) with cardiac abnormalities and 25 (1.7%) with myocarditis/suspected myocarditis. Cardiac involvement in pediatric IgAV mainly manifested as elevated cardiac biomarker levels (n = 162), electrocardiogram abnormalities (n = 46), and echocardiogram/chest X-ray abnormalities (n = 15); however, cardiac-related symptoms were only observed in 15.1% of patients with cardiac involvement. Multivariate analysis demonstrated that interval from disease onset to diagnosis > 7days (OR, 2.157; 95% CI, 1.523-3.057; p < 0.001), IgAV with multi-organ involvement (OR, 1.806; 95% CI, 1.242-2.627; p = 0.002), and elevated D-dimer levels (OR, 1.939; 95% CI, 1.259-2.985; p < 0.001) were independent risk factors for cardiac involvement in pediatric IgAV. The length of hospital stay was significantly longer in the myocarditis/suspected myocarditis group compared with the other two groups (p < 0.05). Conclusion:This study suggests that cardiac involvements in pediatric IgAV is non-negligible, and cardiac involvement is associated with interval from disease onset to diagnosis > 7days, IgAV with multi-organ involvement, and elevated D-dimer levels. Severe cardiac involvement may affect the prognosis of pediatric IgAV. What is Known: • Immunoglobulin A vasculitis (IgAV) is the most common form of systemic vasculitis affecting children and adolescents, which exhibits diverse clinical manifestations. Cases of severe IgAV complicated by cardiac involvement have been anecdotally reported. What is New: • The present study suggests that cardiac involvements in pediatric IgAV is non-negligible, and cardiac involvement is associated with interval from disease onset to diagnosis > 7days, IgAV with multi-organ involvement, and elevated D-dimer levels. Severe cardiac involvement may affect the prognosis of pediatric IgAV.

Correlation between antiphospholipid antibodies and renal involvement in children with Henoch-Schönlein purpura: A cross-sectional study.

Renal involvement is the most damaging long-term complication of Immunoglobulin-A (IgA) vasculitis. In the lack of a definite predictive biomarker for renal involvement, antiphospholipid antibodies (aPL) have been proposed in recent years. In this prospective cohort of 48 pediatric patients who were admitted with IgA vasculitis from September 2015 to June 2017, two serum samples were taken 12 weeks apart to detect Anti-Phospholipid antibodies. All patients were followed-up for renal involvement for six months. Renal involvement occurred in 14 out of 48 patients with IgA vasculitis (29.16%). APLs were positive in nine out of 14 patients with IgA vasculitis and renal involvement (64.28%), in contrast to only six out of 34 patients with IgA vasculitis without renal involvement (17.64%). The presence of aPL antibodies was statistically associated with renal involvement (P=0.002). Although, the relationship between both sex (P=0.025) and age (P=0.046) with aPL positivity was statistically significant, performing a modified logistic regression test, the odds ratio was significant between the groups with and without renal involvement only in term of age and aPL positivity). The presence of aPL antibodies was statistically associated with renal involvement. We found a significant relationship between the age and aPL positivity. Hence, we need multicenter, more extensive cohort studies to reach a better and more accurate conclusion on the relationship between serum aPLs and renal involvement in IgA vasculitis patients.

Mucosal Immune Defence Gene Polymorphisms as Relevant Players in the Pathogenesis of IgA Vasculitis?

ITGAM-ITGAX (rs11150612, rs11574637), VAV3 rs17019602, CARD9 rs4077515, DEFA (rs2738048, rs10086568), and HORMAD2 rs2412971 are mucosal immune defence polymorphisms, that have an impact on IgA production, described as risk loci for IgA nephropathy (IgAN). Since IgAN and Immunoglobulin-A vasculitis (IgAV) share molecular mechanisms, with the aberrant deposit of IgA1 being the main pathophysiologic feature of both entities, we assessed the potential influence of the seven abovementioned polymorphisms on IgAV pathogenesis. These seven variants were genotyped in 381 Caucasian IgAV patients and 997 matched healthy controls. No statistically significant differences were observed in the genotype and allele frequencies of these seven polymorphisms when the whole cohort of IgAV patients and those with nephritis were compared to controls. Similar genotype and allele frequencies of all polymorphisms were disclosed when IgAV patients were stratified according to the age at disease onset or the presence/absence of gastrointestinal or renal manifestations. Likewise, no ITGAM-ITGAX and DEFA haplotype differences were observed when the whole cohort of IgAV patients, along with those with nephritis and controls, as well as IgAV patients, stratified according to the abovementioned clinical characteristics, were compared. Our results suggest that mucosal immune defence polymorphisms do not represent novel genetic risk factors for IgAV pathogenesis.

Does age at disease onset affect the clinical presentation and outcome in children with immunoglobulin A vasculitis?

The study aimed to determine whether there is a relationship between the age at diagnosis and the clinical, laboratory, and prognostic features in pediatric immunoglobulin A vasculitis (IgAV) patients. In this study, 539 pediatric IgAV patients (298 males, 241 females; mean age: 7.74±3.36 years; range, 1 to 17.8 years) were retrospectively evaluated between January 2005 and July 2020. The relationship between clinical findings and age at diagnosis was analyzed by univariate logistic regression analysis. Factors associated with renal involvement, steroid-dependent or refractory disease, and recurrence were examined. The median age of diagnosis was 7.1 (1-17.8) years in all patients. At the time of admission, purpura, abdominal pain, and arthritis were the most common clinical findings. At the time of diagnosis, there was a positive association between age and purpura and an inverse association with the presence of arthritis. There were associations between renal involvement and age at diagnosis (odds ratio=1.22, 95% confidence interval 1.13-1.31, p<0.001), follow-up time (p<0.001), no history of previous infection (p<0.001), and presence of gastrointestinal (GI) involvement (p=0.003). Significant relationships were found between the age at diagnosis, follow-up time, GI involvement, renal involvement, scrotal involvement, the C-reactive protein value at the time of diagnosis, and the presence of steroid-dependent disease. An association was found between recurrence and GI involvement. All refractory patients had renal involvement. Age at diagnosis (p<0.001) and follow-up time (p<0.001) was found to be associated with refractory disease. Age at diagnosis and follow-up time may be associated with renal involvement and refractory and steroid-dependent disease in IgAV. In addition, there may be a relationship between steroid-dependent disease and renal, GI, and scrotal involvement and between GI involvement and recurrence.

Association of the Monocyte-to-High-Density Lipoprotein Cholesterol Ratio with Gastrointestinal Involvement of Immunoglobulin a Vasculitis.

To illustrate the association of monocyte to high-density lipoprotein cholesterol ratio (MHR) and other serum indicators with the pathogenesis and prognosis of immunoglobulin A vasculitis (IgAV) patients in different subgroups. A total of 158 adult patients and 113 healthy controls were enrolled, and the clinical presentation and laboratory indexes were comprehensively assessed. IgAV patients show significantly elevated levels of inflammatory parameters and lipid profiles compared to healthy controls (P < 0.05). Higher levels of the MHR and other normal inflammatory indicators were found in patients with Gastrointestinal (GI) involvement compared to other subgroups. And in group with GI involvement, significantly higher white blood cell (WBC), neutrophil, complement 4 (C4), NLR (neutrophil-to-lymphocyte ratio) and PLR (platelet-to-lymphocyte ratio) levels and lower levels of apolipoprotein-a (Apo-a) were observed. Their correlation analysis demonstrated positive results between MHR level and white blood cell (WBC) count (r = 0.416, P = 0.034), D-Dimer (r = 0.464, P = 0.026) and monocyte (r = 0.947, P < 0.001). And the time until first remission of skin purpura was shown positively correlated with their age (r = 0.456, P = 0.043), C-reactive protein (CRP) level (r = 0.641, P = 0.018), D-Dimer level (r = 0.502, P = 0.040) while negatively correlated with albumin (Alb) level (r=-0.626, P = 0.003) and low-density lipoprotein (LDL) level (r=-0.478, P = 0.033). Our study suggests that those biomarkers represented for inflammatory responses, lipid profile and immunological functions have significant differences in the subgroups of adult IgAV patients. In addition, we also found that MHR level may serve as a potential biomarker for the pathogenesis and prognosis of IgAV patients with GI involvement.

Acute pancreatitis associated with immunoglobulin A vasculitis: report of fifteen cases.

Immunoglobulin A vasculitis (IgAV) is a systemic small vessel vasculitis common in children. Pancreatic involvement in IgAV is rare. The purpose of this study was to analyze the clinical characteristics of IgAV-related acute pancreatitis in children. Records of patients with IgAV-related acute pancreatitis admitted to our institution between January 2016 and December 2019 were reviewed. We summarized the clinical characteristics, laboratory characteristics, imaging findings, treatment, and outcomes of 15 children with IgAV-related acute pancreatitis. The patients' median age was 9.6years. Pancreatitis was the initial manifestation of IgAV in 3 patients. All patients had abdominal manifestations, including abdominal pain (15/15), vomiting (10/15), and gastrointestinal bleeding (7/15). Serum amylase and lipase levels were elevated in all patients. Serum amylase in 4 cases reached more than three-fold elevation and serum lipase in 14 cases reached more than three-fold elevation. Morphological abnormalities and abnormal signals of the pancreas were observed in 13 cases by magnetic resonance imaging. Pancreaticobiliary maljunction was seen in 3 cases by magnetic resonance cholangiopancreatography. Glucocorticoid therapy and intravenous immunoglobulins were used to treat acute pancreatitis in IgAV. All patients showed clinical improvement after treatment. During the follow-up period of 6-12months, all 15 cases with pancreatitis were cured without recurrence. Pancreatic involvement is rare in IgAV; however, this should be considered in IgAV patients with severe abdominal pain. The timely application of steroid therapy is important for IgAV-associated pancreatitis. Key Points • Acute pancreatitis is a rare complication of immunoglobulin A vasculitis (IgAV). • Acute pancreatitis can be the initial manifestation of IgAV. It is important to evaluate for pancreatitis while IgAV patients with severe abdominal pain. • A common image finding of IgAV-associated pancreatitis was swelling of the pancreas. • Glucocorticoid therapy and intravenous immunoglobulins is helpful in alleviating acute pancreatitis in IgAV.

IgA Vasculitis: Influence of CD40, BLK and BANK1 Gene Polymorphisms.

CD40, BLK and BANK1 genes involved in the development and signaling of B-cells are identified as susceptibility loci for numerous inflammatory diseases. Accordingly, we assessed the potential influence of CD40, BLK and BANK1 on the pathogenesis of immunoglobulin-A vasculitis (IgAV), predominantly a B-lymphocyte inflammatory condition. Three genetic variants within CD40 (rs1883832, rs1535045, rs4813003) and BLK (rs2254546, rs2736340, rs2618476) as well as two BANK1 polymorphisms (rs10516487, rs3733197), previously associated with inflammatory diseases, were genotyped in 382 Caucasian patients with IgAV and 955 sex- and ethnically matched healthy controls. No statistically significant differences were observed in the genotype and allele frequencies of CD40, BLK and BANK1 when IgAV patients and healthy controls were compared. Similar results were found when CD40, BLK and BANK1 genotypes or alleles frequencies were compared between patients with IgAV stratified according to the age at disease onset or to the presence/absence of gastrointestinal or renal manifestations. Moreover, no CD40, BLK and BANK1 haplotype differences were disclosed between patients with IgAV and healthy controls and between patients with IgAV stratified according to the clinical characteristics mentioned above. Our findings indicate that CD40, BLK and BANK1 do not contribute to the genetic background of IgAV.

Biologics for immunoglobulin A vasculitis: targeting vasculitis or comorbid disease?

In this study, we aimed to evaluate the clinical features and treatments, including the use of biological disease-modifying anti-rheumatic drugs (bDMARDs) in a large cohort of pediatric and adult immunoglobulin A vasculitis (IgAV). Since data on the use of bDMARDs in IgAV are very limited, we collated the reasons for use of bDMARDs during the disease course. Patients who were enrolled in the Hacettepe University Vasculitis Research Centre (HUVAC) registry were included. In this prospective database dating from 2014, there were 436 IgAV patients classified as IgAV according to Ankara 2008 and/or American College of Rheumatology 1990 criteria. 88 adults and 330 pediatric IgAV patients were included as the main study group. Concomitant spondyloarthritis (SpA) was observed only in adult patients (10% vs 0% in children, p < 0.001). IgAV relapse was more common in adults than in children (p: 0.017). Adult patients were mostly treated with corticosteroid (p < 0.001) and conventional synthetic disease-modifying anti-rheumatic drug treatment (< 0.001), while more than half of the pediatric patients were followed up without immunosuppressive treatment. Ten (11%) adult patients used biologics. Among them, two patients used rituximab due to IgAV disease activity, three used infliximab due to SpA, three used etanercept due to SpA (one patient had a pediatric onset enthesitis-related arthritis), and two used anakinra due to recurrent familial Mediterranean fever attacks. This is the first study evaluating the use of all bDMARDs for any reason in the IgAV cohorts in the literature. None of the pediatric patients used biologics. Our data suggest biologics are mainly used for comorbid inflammatory diseases over refractory vasculitis in adult IgAV.

Prognostic Value of C4d Immunolabelling in Adult Patients With IgA Vasculitis.

Background and Objectives: Glomerular C4d deposits are associated the severity and outcomes of IgA nephropathy. Whether this holds true in immunoglobulin A vasculitis (IgAV) is not known. The main objective of the study was to analyze the prognostic value of glomerular C4d immunolabelling on kidney impairment in adults with IgAV.Design, Setting, Participants, Measurements: This retrospective cohort study included 120 adults with IgAV and a kidney biopsy performed between 1995 and 2018 in two French university hospital centers. All paraffin-embedded biopsies were reassessed according to Oxford classification. Immunofluorescence for C4d was performed in all cases. For analysis, patients were grouped according to positivity for C4d in the glomerular area. The main outcome was a composite endpoint of 50% increase in 24 h-proteinuria, or eGFR decrease by 50%, or kidney replacement therapy.Results: The median follow-up was 28.3 months. Twenty-three patients met the composite endpoint, 12 for kidney replacement therapy, 6 for an eGFR decrease >50% and 5 for a >50% increase in proteinuria. At time of biopsy, the median proteinuria was 1.9 g/24 h and the median eGFR 73.5 mL/min/1.73 m2. Among the 102 patients evaluable for C4d, 24 were positive on >30% glomeruli, mainly with a parieto-mesangial pattern. In this group, the initial proteinuria was more frequently nephrotic than in the C4d– group (60% vs. 33%, P = 0.039). Mesangial hypercellularity was more frequent in the C4d+ group (42% vs. 13%; P = 0.006) whereas macroscopic hematuria was more frequent in the C4d– group (18% vs. 0%; P = 0.03). After a median follow-up of 28 months, kidney survival did not differ according to C4d status.Conclusion: In a population of adult IgAV patients, glomerular positivity for C4d was associated with the severity of the kidney disease at presentation, but not with subsequent renal function deterioration.

Correlations of Serological Markers with Development of Systemic Involvement in Adult Immunoglobulin A Vasculitis: A Retrospective Study of 259 Patients in Central China.

Although relatively rare, adult immunoglobulin A vasculitis (IgAV) can lead to severe complications and longer hospitalization, and result in poor prognosis, when compared to childhood IgAV. Hence, early identification and prevention for patients prone to develop systemic involvement are essential. The purpose of this study was to explore the correlations of common serological markers with the development of systemic involvement in adult IgAV. A retrospective analysis was performed for adult IgAV patients, who were hospitalized in Wuhan Union Hospital between January 2016 and December 2019. A total of 259 patients were enrolled, and the pre-treatment serological markers were comprehensively assessed. In the present study, 49.0% and 33.2% of patients developed renal and gastrointestinal (GI) involvement, respectively. Furthermore, the elevated levels of white blood cells count, D-Dimer (D-D), C-reactive protein (CRP) and neutrophil granulocyte ratio (NE%) >60% were significantly associated with GI involvement in the univariate analysis, while the decrease in high density lipoprotein level, and the elevated D-D and CRP levels were significantly associated with renal involvement (P<0.05). Moreover, a prediction model that combined multiple markers was established by performing a logistic regression analysis, and this presented a more favorable value of prediction than the individual serological markers. The present study suggests that common serological markers have close correlations with systemic involvement in adult IgAV, and that the establishment of a prediction model for systemic involvement may be helpful in facilitating personalized therapeutic strategies and clinical management for IgAV patients.

Role of the IL33 and IL1RL1 pathway in the pathogenesis of Immunoglobulin A vasculitis

Cytokines signalling pathway genes are crucial factors of the genetic network underlying the pathogenesis of Immunoglobulin-A vasculitis (IgAV), an inflammatory vascular condition. An influence of the interleukin (IL)33- IL1 receptor like (IL1RL)1 signalling pathway on the increased risk of several immune-mediated diseases has been described. Accordingly, we assessed whether the IL33-IL1RL1 pathway represents a novel genetic risk factor for IgAV. Three tag polymorphisms within IL33 (rs3939286, rs7025417 and rs7044343) and three within IL1RL1 (rs2310173, rs13015714 and rs2058660), that also were previously associated with several inflammatory diseases, were genotyped in 380 Caucasian IgAV patients and 845 matched healthy controls. No genotypes or alleles differences were observed between IgAV patients and controls when IL33 and IL1RL1 variants were analysed independently. Likewise, no statistically significant differences were found in IL33 or IL1RL1 genotype and allele frequencies when IgAV patients were stratified according to the age at disease onset or to the presence/absence of gastrointestinal (GI) or renal manifestations. Similar results were disclosed when IL33 and IL1RL1 haplotypes were compared between IgAV patients and controls and between IgAV patients stratified according to the clinical characteristics mentioned above. Our results suggest that the IL33-IL1RL1 signalling pathway does not contribute to the genetic network underlying IgAV.

BAFF, APRIL and BAFFR on the pathogenesis of Immunoglobulin-A vasculitis

BAFF, APRIL and BAFF-R are key proteins involved in the development of B-lymphocytes and autoimmunity. Additionally, BAFF, APRIL and BAFFR polymorphisms were associated with immune-mediated conditions, being BAFF GCTGT>A a shared insertion-deletion genetic variant for several autoimmune diseases. Accordingly, we assessed whether BAFF, APRIL and BAFFR represent novel genetic risk factors for Immunoglobulin-A vasculitis (IgAV), a predominantly B-lymphocyte inflammatory condition. BAFF rs374039502, which colocalizes with BAFF GCTGT>A, and two tag variants within APRIL (rs11552708 and rs6608) and BAFFR (rs7290134 and rs77874543) were genotyped in 386 Caucasian IgAV patients and 806 matched healthy controls. No genotypes or alleles differences were observed between IgAV patients and controls when BAFF, APRIL and BAFFR variants were analysed independently. Likewise, no statistically significant differences were found in the genotype and allele frequencies of BAFF, APRIL or BAFFR when IgAV patients were stratified according to the age at disease onset or to the presence/absence of gastrointestinal (GI) or renal manifestations. Similar results were disclosed when APRIL and BAFFR haplotypes were compared between IgAV patients and controls and between IgAV patients stratified according to the clinical characteristics mentioned above. Our results suggest that BAFF, APRIL and BAFFR do not contribute to the genetic network underlying IgAV.

The Relationship Between IgA Vasculitis and Antioxidant Activity In Children

Objective: Immunoglobulin A vasculitis (IgAV) is the most common systemic vasculitis seen in children. The aim of this study is to investigate the relationship between malondialdehyde-induced oxidative stress, antioxidant system and organ involvement in IgAV patients. Method: 32 patients and 28 healthy children were included in the study. Serum malondialdehyde, reduced glutathione, vitamin E, vitamin C, retinol, and beta-carotene levels were measured in patients (separately in both the active and remission phases) and healthy children. Results: MDA levels were significantly higher in patients with active phase while reduced glutathione and vitamin C levels were markedly lower in both the active and the remission phases. Retinol and beta-carotene levels were lower in the active phase. It was found that retinol levels were significantly lower in patients with gastrointestinal system involvement compared to those without. Vitamin C levels were significantly lower in those with kidney involvement compared to those without. Also, a negative correlation was observed between retinol levels and the number of organs involved. Conclusion: We consider that especially vitamin C and vitamin A may be used in the treatment of IgAV. However, whether the derangements of the oxidant/antioxidant balance in the direction of increased oxidative stress are consequences or causes of the events occurring in the active phase of IgAV are open to further investigation.

Serum VEGF-A and VEGFR-1 levels in patients with adult immunoglobulin A vasculitis.

Immunoglobulin A vasculitis (IgAV) is classified as a leukocytoclastic vasculitis characterized by immune deposits in endothelial walls of small vessels causing vascular endothelial injury. The aim of the present study is to evaluate levels of vascular endothelial growth factor-A (VEGF-A) and VEGF receptor-1 (VEGFR-1) levels in adult IgAV patients. Thirty-seven adult IgAV patients admitted to the Rheumatology Clinic meeting the IgAV American College of Rheumatology (ACR) criteria and 32 control subjects were enrolled in the study. Disease activity was categorized as "remission" or "active" according to Birmingham Vasculitis Activity Score (BVAS). Serum VEGF-A, VEGFR-1 levels and VEGFR-1/VEGF-A ratio were evaluated in patient and control groups. Serum median VEGF-A, VEGFR-1 and VEGFR-1/VEGF-A ratios were significantly higher in the patient group when compared to controls (235.9 [155-308.4] pg/mL vs. 78.8 [29.7-210.3] pg/mL, 400 [277.2-724.3] pg/mL vs. 31.5 [12.5-214.4] pg/mL and 1.85 [0.57-2.97] vs. 0.46 [0.38-0.63] respectively, all P values <.001). VEGFR-1 had the strongest predictive value with a cut-off value of 0.6 with 75% sensitivity and 73% specificity (P<.001). This study is the first report indicating elevated serum VEGF-A, VEGFR-1, and more importantly VEGFR-1/VEGF-A ratio can be good representatives of the inflammatory processes together with vascular endothelial injury in adult IgAV patients. VEGFR-1 seems to be a more important indicator of the ongoing inflammation.

Metagenomic profiling reveals dominance of gram-positive bacteria in the gut microbiome shifts associated with immunoglobulin A vasculitis (Henoch-Schönlein Purpura).

ObjectivesImmunoglobulin A vasculitis (IgAV), previously known as Henoch–Schönlein purpura, is the most common vasculitis that has a classical skin manifestation of palpable purpuric rash. Factors pertinent to IgAV remain inadequately understood. Here, we aimed to examine the gut microbiome shifts associated with IgAV and its recovery.MethodsStool samples were collected from 10 children with IgAV (6–14 years old) before and after a multi‐drug therapy, along with 9 age‐matched healthy children. The samples were subjected to metagenomic analyses to investigate the taxonomic and functional shifts of the gut microbiome.ResultsThe analyses revealed that compared with healthy controls, treatment‐naïve patients exhibited substantial taxonomic and functional alterations of gut microbiota, including 104 IgAV‐depleted species and 7 IgAV‐elevated species (FDR < 0.05). After treatment, the IgAV patients displayed a partial restoration of the microbiota shifts, as the relative abundances of some biomarkers (e.g. 9 genera and 22 species) became comparable (FDR > 0.1) between the patients and healthy controls. The treatment‐responsive features included Weissella, Faecalibacterium prausnitzii and Bifidobacterium pseudocatenulatum and three components of a putative glutamine transport system. Importantly, gram‐positive bacteria accounted for over 85% of the numbers and total relative abundance of the species that were associated with IgAV and responsive to the treatment. In addition, of the 122 IgAV‐depleted bacterial genes, 82 were mainly contributed by gram‐positive bacteria and 12 by gram‐negative bacteria.ConclusionsGram‐positive bacteria are the main drivers underlying the gut microbiome shifts of IgAV, which may assist rational management of the disease.

Onset age is a risk factor for refractory pediatric IgA vasculitis: a retrospective cohort study

BackgroundThough outcome differences between children and adults with immunoglobulin A vasculitis (IgAV) has been well documented, it remains unclear if disease features in pediatric IgAV patients vary with onset age. We aimed to explore clinical features and prognosis of pediatric IgAV stratified by onset age.MethodsWe retrospectively reviewed records of patients under 18 years old diagnosed with IgAV from January 1999 to December 2018 in one tertiary medical center in Taiwan. Patients were grouped by onset age: ≤ 6 years old, 6–12 years old (> 6, ≤ 12), and 12–18 years old (> 12, < 18). Demographics, laboratory data, incidence of gastrointestinal, renal, and joint involvement, corticosteroid dependence, recurrence, and refractory disease were analyzed. Recurrence was defined as disease flare-up after complete remission and discontinuation of all medications for at least 3 months. Corticosteroid dependence was defined by more than 6 weeks of daily oral corticosteroid intake. Refractory disease was defined as not achieving complete remission 6 months after disease onset. Statistical analysis was performed using R software (v3.6.0).ResultsThere were 484 IgAV patients, with an onset age of 6.10 (4.72–8.58) (median (IQR)) years old. There were 234 (48.3%) patients ≤6 years old, 210 (43.4%) 6–12 years old, and 40 (8.3%) 12–18 years old. One hundred and thirty (26.9%) patients had renal involvement, which was more frequent in older children (≤ 6 years old, 18.4%; 6–12 years old, 31.0%; 12–18 years old, 55.0%; p < 0.001). There were 361 patients (74.6%) with joint involvement; younger children were affected more frequently (≤ 6 years old, 82.1%; 6–12 years old, 71.9%; 12–18 years old, 45.0%; p < 0.001). Gastrointestinal involvement was present in 311 (64.3%) patients, showing no difference among age groups. There were 46 patients (9.5%) with recurrent IgA vasculitis, 136 (28.1%) with corticosteroid dependent and 76 (15.7%) with refractory disease. Corticosteroid dependence and refractory disease occurred more frequently as onset age increased (p < 0.001).ConclusionPediatric IgAV with different onset ages are associated with distinct clinical manifestations and outcomes. The risk of developing corticosteroid dependence, refractory disease and renal involvement increased with onset age.

Rituximab treatment for IgA vasculitis: A systematic review.

Immunoglobulin A vasculitis (IgAV) is a systemic small vessel vasculitis for which treatment of severe cases is usually based on glucocorticoids and other conventional immunosuppressive drugs. The role of rituximab for resistant or refractory cases has been explored in isolated case reports and small series. To perform a literature review of all pediatric and adult patients with IgAV treated with rituximab (RTX) and to assess disease characteristics, RTX efficacy and safety. We conducted a systematic literature review according to PRISMA guidelines by selecting articles with information on IgAV and RTX up to October 2019. We extracted data on patient characteristics, disease course, RTX efficacy and tolerance. The resulting database was analyzed with statistical software package SPSS v 22.0. Among the initial 161 articles found, 20 studies including 35 well-characterized IgAV patients treated with RTX were finally analyzed. Distribution by sex was similar, and the median age at diagnosis was 26 (range: 2 months to 70 years). Patients included were equally diagnosed at pediatric age and in the adulthood. Almost 90% of patients had renal involvement before RTX treatment and resistant or refractory disease to glucocorticoids or other immunosuppressive agents, mainly with renal impairment, was the reason for RTX administration in 85.7% of patients. RTX was used because of contraindication to these previous agents in 8.6% of patients, and as first line therapy in 5.7% of them. With regard to RTX response, 94.3% of patients presented clinical improvement of any type and 74.3% achieved sustained remission at the end of follow-up. Among the 13 (37.1%) patients who experienced a disease relapse, 11 (31.4%) were treated with a new RTX dose, with good disease control in all cases. In terms of treatment requirements, glucocorticoids and additional immunosuppressants were significantly lower after RTX administration. No deaths were observed and the rate of minor RTX-associated adverse effects was of 8.6%. RTX seems to be a safe and useful agent in inducing disease remission and reducing previous immunosuppressive treatment in IgAV pediatric and adult patients resistant or refractory to glucocorticoids or other immunosuppressive drugs, and in those patients in whom these agents are contraindicated. Nevertheless, controlled clinical trials in are still warranted to clarify the role of RTX in IgAV.