Association of IL1R polymorphism with HLA-B27 positive in Iranian patients with ankylosing spondylitis

Ankylosing spondylitis (AS) is one of the most common causes of inflammatory arthritis, with an estimated prevalence of 0.1-0.9%. Genetic factors have been strongly implicated in its aetiology, and heritability as assessed by twin studies has been estimated to be >90%. HLA- B27 is almost essential for inheritance of AS; it is not merely sufficient for explaining the pattern of familial recurrence of the disease. This study's purpose is to investigate the association of ankylosing spondylitis with single-nucleotide polymorphisms (SNPs) in the IL-1 family: IL-1a (-889C/T) rs1800587, IL-1b (-511C/T) rs16944, IL-1b (+3962C/T) rs1143634, IL-1R (Pst-1 1970C/T) rs2234650 and IL-1RA (Mspa-1 11100C/T) rs315952. 99 unrelated Iranian AS patients and 217 healthy control subjects were selected. Cytokine typing was performed by the polymerase chain reaction with sequence-specific primers assay. The allele and genotype frequencies of the polymorphisms were determined: The IL1α rs1800587, IL1β rs16944 and IL1β rs1143634 were not significantly associated with AS. Genotype frequencies at IL1R rs2234650 differed between cases and controls (χ(2)=8.85; p=0.01); the IL1R rs2234650 C/T and T/T genotypes were less common in AS patients than controls. The IL1R rs2234650 C/T genotype was inversely associated with AS comparing with the IL1R rs2234650 C/C genotype (OR=0.48; p=0.005). IL1R rs2234650 C/T genotype was less common in patients than controls (OR=0.37; p=0.02).Furthermore IL1R rs2234650 T allele was strongly associated with HLA-B2702 patients rather than HLA-B2705 but was not associated with HLA-B27 negative patients (OR=0.33; p=0.01). Polymorphisms of IL1α rs1800587, IL1β rs16944 and IL1β rs1143634 were not significantly associated with ankylosing spondylitis but inversely in this study IL1R rs2234650 was significantly associated and carriage of T allele in IL1R rs2234650 seems to be protective, while carriage of C allele result in two fold higher risk of developing AS.     

Association of the sEH gene promoter polymorphisms and haplotypes with preeclampsia

BackgroundThe epoxyeicosatrienoic acids (EETs) have antihypertensive, anti-inflammatory, and organ protective properties and their circulation levels are related to hypertension, diabetes mellitus, cardiovascular diseases, and preeclampsia. Soluble epoxide hydrolase (sEH) catalyses the degradation of EETs to less biologically active dihydroxyeicosatrienoic acids. Here, we sequenced the promoter region of EPHX2 to investigate the association between promoter sequence alterations that we thought to affect the expression levels of the enzyme and preeclampsia (PE).MethodsNucleotide sequencing of the promoter region of the EPHX2, spanning from position -671 to +30, was performed on 100 pregnant women with PE and, 20 or more weeks pregnant normotensive, healthy women (n=100).ResultsPregnant women who carry rs4149235, rs4149232, rs73227309, and rs62504268 polymorphisms have 4.4, 2.4, 2.3, and 2.8 times significantly increased risk of PE, respectively. CCGG (OR: 3.11; 95% CI: 1.12-8.62) and CCCA (OR: 0.45; 95% CI: 0.36-0.55) haplotypes were associated with an increased and decreased risk of PE, respectively.ConclusionsFour SNPs (rs4149232, rs4149235, rs73227309, and rs62504268) in the promoter region of the EPHX2, and CCGG and CCCA haplotypes of these 4 SNPs were significantly associated with PE. These SNPs in the promoter region may affect sEH expression and thus enzyme activity and may play a role in PE pathogenesis by causing individual differences in EET levels. However, future studies are needed to confirm our findings and examine the effect of these SNPs on the sEH expression and/or enzyme activity.     

Retracted: Rs11655237 polymorphism of LINC00673 affects the prognosis of cervical cancer by interfering with the interaction between LINC00673 and microRNA-1231

Single-nucleotide polymorphism (SNP) in long noncoding RNAs (lncRNAs) is known to disrupt the binding between lncRNAs and microRNAs. In this paper, we aimed to explore the role of LINC00673 rs11655237 SNP in the survival of cervical cancer (CC). Real-time polymerase chain reaction and western-blot analysis were used to detect expressions of LINC00673 and microRNA-1231 (miR-1231) in CC patients with different rs11655237 SNP genotypes. And the expression of LINC00673, miR-1231, and IFNAR1 was measured in mice and cells treated with exosomes carrying GG, GA, and AA rs11655237 genotypes. Compared with patients carrying the rs11655237 A allele of LINC00673 rs11655237 SNP, patients carrying the G allele showed higher overall survival and higher miR-1231 expression. In addition, the expression of miR-1231 was the highest in patients carrying the GG genotype and the lowest in patients carrying the AA genotype. Furthermore, the exosomes carrying GG, GA, and AA genotypes of LINC00673 rs11655237 SNP reduced tumor growth in mice, while the inhibitory effect of rs11655237 A allele was much stronger than that of the rs11655237 G allele. Additionally, exosome treatment upregulated the expression of LINC000673 and IFNAR1 while downregulating the expression of miR-1231. Interestingly, the A allele of rs11655237 generated a binding site for miR-1231 and subsequently affected the expression of IFNAR1, a target gene of miR-1231 containing a miR-1231 binding site in its 3′-untranslated region. Cells transfected with exosomes carrying GG, GA, and AA genotypes of LINC00673 rs11655237 SNP achieved higher LINC000673 and IFNAR1 expression along with lower miR-1231 expression. Therefore, rs11655237 can be used as a prognostic biomarker for CC.     

Interleukin 4 receptor is associated with an increase in body mass index in Koreans

A body of evidence indicates obesity is an inflammatory state with chronic activation of the immune system. The interleukin 4 receptor (IL4R) single nucleotide polymorphism (SNP), rs 180275 (1902A>G) is well recognized for its association with atopy and other inflammatory diseases. We assessed the possible association of rs 180275 and rs 1805010 with obesity in Korean population. Study subject consisting of 876 Koreans were divided into three groups: subjects with 1) BMI<25, 2) BMI between 25 and 27, and 3) BMI>27. Analyses of genotype distributions and allele frequencies of study subjects revealed that rs 180275 polymorphism was associated with an increase in BMI in Korean population (P=0.009 and 0.011, respectively) while no association was found between rs 1805010 and obesity. We observed significantly lower percentage of rs 180275 G allele in subjects with BMI>27 than in subjects with BMI< or =27 (9.9% vs. 16.0%). Logistic regression analysis revealed that the odds ratio (OR) for an increase in BMI associated with the G vs. A allele was 0.57 [95% Confidence interval (CI)=0.39-0.85, p=0.002], which strongly implicates the protective role of rs 180275 G allele against an increase in BMI. Haplotype analysis revealed no association was present between rs 180275 and rs 1805010 polymorphisms. The frequency of rs 180275 G allele is significantly lower in subjects with BMI>27, suggesting the protective role of IL4R rs 180275 G allele against an increase in BMI in Korean population.     

Putative EPHX1 enzyme activity is related with risk of lung and upper aerodigestive tract cancers: a comprehensive meta-analysis

Background

EPHX1 is a key enzyme in metabolizing some exogenous carcinogens such as products of cigarette-smoking. Two functional polymorphisms in the EPHX1 gene, Tyr113His and His139Arg can alter the enzyme activity, suggesting their possible association with carcinogenesis risk, particularly of some tobacco-related cancers.

Methodology/Principal Findings

A comprehensive systematic review and meta-analysis was performed of available studies on these two polymorphisms and cancer risk published up to November 2010, consisting of 84 studies (31144 cases and 42439 controls) for Tyr113His and 77 studies (28496 cases and 38506 controls) for His139Arg primarily focused on lung cancer, upper aerodigestive tract (UADT) cancers (including oral, pharynx, larynx and esophagus cancers), colorectal cancer or adenoma, bladder cancer and breast cancer. Results showed that Y113H low activity allele (H) was significantly associated with decreased risk of lung cancer (OR = 0.88, 95%CI = 0.80–0.96) and UADT cancers (OR = 0.86, 95%CI = 0.77–0.97) and H139R high activity allele (R) with increased risk of lung cancer (OR = 1.18, 95%CI = 1.04–1.33) but not of UADT cancers (OR = 1.05, 95%CI = 0.93–1.17). Pooled analysis of lung and UADT cancers revealed that low EPHX1 enzyme activity, predicted by the combination of Y113H and H139R showed decreased risk of these cancers (OR = 0.83, 95%CI = 0.75–0.93) whereas high EPHX1 activity increased risk of the cancers (OR = 1.20, 95%CI = 0.98–1.46). Furthermore, modest difference for the risk of lung and UADT cancers was found between cigarette smokers and nonsmokers both in single SNP analyses (low activity allele H: OR = 0.77/0.85 for smokers/nonsmokers; high activity allele R: OR = 1.20/1.09 for smokers/nonsmokers) and in combined double SNP analyses (putative low activity: OR = 0.73/0.88 for smokers/nonsmokers; putative high activity: OR = 1.02/0.93 for smokers/ nonsmokers).

Conclusions/Significance

Putative low EPHX1 enzyme activity may have a potential protective effect on tobacco-related carcinogenesis of lung and UADT cancers, whereas putative high EPHX1 activity may have a harmful effect. Moreover, cigarette-smoking status may influence the association of EPHX1 enzyme activity and the related cancer risk.     

LG3 fragment of endorepellin is a possible biomarker of severity in IgA nephropathy

IgA nephropathy (IgAN), the most common primary glomerulonephritis, is characterized by deposition of IgA in the glomerular mesangium. The diagnosis of IgAN still requires a kidney biopsy that cannot easily be repeated in the same patient during follow‐up. Therefore, identification of noninvasive urinary biomarkers would be very useful for monitoring patients with IgAN. We first used bidimensional electrophoresis (2DE) coupled to MALDI‐TOF‐TOF and Western blot to identify some urinary biomarkers associated with IgAN. Urine of IgAN patients showed an increase of albumin fragments, α‐1‐antitrypsin and α‐1‐β‐glycoprotein, along with a decrease of a single spot that was identified as the laminin G‐like 3 (LG3) fragment of endorepellin. The urinary proteomes of 43 IgAN patients were compared to those of 30 healthy individuals by ELISA. Quantification of LG3 confirmed a significant decrease in the urine of IgAN patients compared to healthy controls, except in ten patients in whom LG3 was increased. These ten patients had a more severe disease with lower glomerular filtration rate values. We found a significant inverse correlation between LG3 levels and glomerular filtration rate in the 43 patients with IgAN, which was not observed in 65 patients with other glomerular diseases including membranous nephropathy (23), lupus nephropathy (13), focal segmental glomerulosclerosis (15), diabetic nephropathy (14), and six patients with nonglomerular diseases. Therefore, we suggest that the LG3 fragment of endorepellin could be associated with IgAN severity and might be related to pathogenesis of IgAN.     

Association of rs11801299 and rs1380576 polymorphisms at MDM4 with risk,clinicopathological features and prognosis in patients with retinoblastoma

Backgroundrs11801299 and rs1380576, two novel polymorphisms in MDM4 gene, have been investigated in several different cancer types. However, the role of these two polymorphisms in retinoblastoma (RB) remains unclear.MethodsA total of 126 patients with primary RB and 148 age-/gender-matched controls were included in this retrospective study. The frequency of rs11801299 and rs1380576 were determined between RB patients and controls. The association of these two polymorphisms with clinicopathological characteristics, prognosis were further evaluated.ResultsAA genotype at rs11801299 was significantly associated with an increased risk of developing RB (OR = 2.06, 95%CI 1.09–3.90). The possibility of developing RB was also significantly increased in individuals with A allele at rs11801299 (OR = 1.49, 95%CI 1.06–2.08). RB patients carrying AA genotype and A allele at rs11801299 were more likely to have tumor invasion and poor differentiation. As for rs1380576, a significantly lower risk of developing RB was observed in patients with G allele (CG + GG) compared with wild-type CC genotype (OR = 0.59, 95%CI 0.36–3.95). RB patients with GG genotype or G allele had a lower risk of developing highly aggressive cancer. Kaplan-Meier curves and log-rank results revealed that RB patients carrying AA genotype or A allele (AA + GA) at rs11801299 had significantly poorer prognosis. Multivariate COX analysis showed that the rs11801299 G allele was associated with decreased survival but was not an independent prognostic factor.Conclusionrs11801299 was significantly associated with RB risk, pathological differentiation, tumor aggressiveness and poor prognosis.     

Analysis of MIF,FCGR2A and FCGR3A gene polymorphisms with susceptibility to pulmonary tuberculosis in Moroccan population

In order to investigate the influence of functional polymorphisms of macrophage migration inhibitory factor(MIF),Fcg receptors CD16A(FCGR3A) and CD32A (FCGR2A) genes on susceptibility to pulmonary tuberculosis(PTB)in the Moroccan population,we analyzed 123 patients with PTB and 154 healthy controls.The genotyping for MIF-173(G/C)(rs755622),FCGR2A-131H/R(rsl801274)and FCGR3A-158V/F(rs396991) was carried out using TaqMan SNP Genotyping Assay method.We found a statistically significant increase of the MIF-173CC homozygote genotype and MIF-173*C allele frequencies in PTB patients compared with healthy controls (17.07%versus 5.84%,P=0.003;and 35.37%versus 26.30%,P=0.02;respectively).In contrast,no association was observed between CGR2A-131H/R and FCGR3A-158V/F polymorphisms and tuberculosis disease.Our finding suggests that MIF-173*C variant may play an important role in the development of active tuberculosis.     

Association of Tumor Necrosis Factor Alpha-Induced Protein 3 Interacting Protein 1 (<Emphasis Type="Italic">TNIP1</Emphasis>) Gene Polymorphism (rs7708392) with Lupus Nephritis in Egyptian Patients

Lupus nephritis (LN) is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE). Previous studies suggest that mutant A20 binding inhibitor of NF-κB 1 (ABIN1) protein encoded by tumor necrosis factor alpha-induced protein 3 interacting protein 1 (TNIP1) gene is associated with LN via NF-κB dysregulation. The aim of the current study was to evaluate the association of TNIP1 gene SNP rs7708392 with SLE and LN in Egyptian patients. 5′ nuclease Allelic discrimination was used to evaluate the frequency of TNIP1 SNP rs7708392 in 53 patients with LN, 57 SLE patients without nephritis and 85 healthy controls. The genotyping analysis revealed that the CC genotype was more frequent in controls than SLE patients, while GC and GG genotypes were more common in SLE patients. Moreover, the GG genotype and the G allele were significantly more prevalent among LN patient than non-LN patients (P?<?0.001). In LN patients, the most common genotype was GG (56.6%), while among the non-LN patients; the CG genotype was the most common (59.6%). Regression analysis demonstrated that SLE patients carrying only one G allele had a 3.4 folds increased risk for LN. Our results suggested that TNIP1 SNP (rs7708392) might be associated with the LN in Egyptian SLE patients. TNIP1 SNP (rs7708392) might be used to identify patients at risk of developing LN, which could help in early detection and treatment before progression to end-stage renal disease, improving patients’ outcome and quality of life.     

LINC00205 modulates the expression of EPHX1 through the inhibition of miR-184 in hepatocellular carcinoma as a ceRNA

Several studies have shown that low expression of epoxide hydrolase 1 (EPHX1) is closely associated with varying human cancers, including hepatocellular carcinoma (HCC). This study aims to explore the potential mechanism of EPHX1 silencing and revealed a novel regulatory pathway in the pathogenesis of HCC. In this study, micro ribonucleic acid (miR)-184 was predicted and validated to be a regulator of EPHX1 through experiments, and its expression was negatively correlated with the messenger RNA (mRNA) levels of EPHX1 in primary tumors. Elevation of EPHX1 suppressed cell proliferation and migration as well as cell cycle progression, and induced apoptosis, while downregulation of miR-184 exhibited the opposite effect on cellular processes. Moreover, LINC00205 interacted with miR-184 and was markedly downregulated in tumors. The effects of the miR-184 inhibitor on cell proliferation, apoptosis, and migration were reversed in part by the transfection with LINC00205 small interfering RNAs. In addition, LINC00205 acted as a molecular sponge to positively regulate the mRNA and protein levels of EPHX1 via regulating miR-184. The tumorigenicity of HCC cells was enhanced by LINC00205 shRNA but diminished by overexpression of EPHX1 in vivo. Clinically, the EPHX1 expression in patients with HCC was markedly downregulated. Taken together, the results of this study suggest that as a competing endogenous RNA, LINC00205 may regulate EPHX1 by inhibiting miR-184 in the progression of HCC and that targeting the LINC00205/miR-184/EPHX1 axis may provide a treatment protocol for patients.     

Analysis of <Emphasis Type="Italic">ICAM1</Emphasis> gene polymorphism in Slovak multiple sclerosis patients

Infiltration of immune cells into CNS is one of the essential events in multiple sclerosis (MS) development. Adhesion molecules like the intercellular adhesion molecule 1 (ICAM-1) play critical role in this process. Therefore, the ICAM1 gene containing two important single-nucleotide polymorphisms (SNPs) belongs to candidate loci with possible involvement in MS susceptibility and/or severity. The objective of our case-control study was to analyze the association of two functional ICAM1 polymorphisms rs1799969 (or G241R) and rs5498 (or K469E) with susceptibility to MS and evaluate their influence on the age at disease onset, severity, neurological disability and progression rate. Two hundred forty-eight MS subjects (mean 39.2 years) and 208 age-matched controls (mean 35.6 years) were involved in the study. Genotyping of ICAM1 rs1799969 and rs5498 SNPs was performed by PCR-RFLP. Presence of the rs3135388 polymorphism tagging the major MS risk allele HLA-DRB1*15:01 allele was determined as well. Our analysis revealed no statistically significant association of ICAM1 polymorphisms with risk of MS development in the Slovak population. Stratification of study cohorts by gender, age at onset and presence of the HLA-DRB1*15:01 risk allele showed only moderate changes. Correlation of clinical findings as age at onset, Kurtzke Expanded Disability Status Scale, Multiple Sclerosis Severity Score and progression index with ICAM1 genotypes in MS patients revealed no significant association; however, patients with earlier onset of MS showed slightly higher frequencies of the homozygous G allele at rs5498 in comparison to other genotypes (P = 0.04), suggesting that GG carriers tend to induce MS at an earlier age.     

The association between interleukin-21 (rs2055979G/T) gene polymorphism and the risk of hepatocellular carcinoma and metastasis in patients with hepatitis C virus

Cancer prevalence is critically increasing worldwide; accordingly, improved prediction and therapeutic tools are necessary. Interleukin (IL)-21 is a potent antitumor cytokine, and the relationship between its gene variations and cancer risk is well established. Nevertheless, so far no study has investigated its role in hepatocellular carcinoma (HCC) progression and metastasis in hepatitis C virus (HCV)-infected people. Therefore, the present investigation was led on 267 Egyptian participants, involving 177 patients with HCV of which 90 patients had HCC (HCC group), 87 patients without HCC (non-HCC group), and 90 unrelated healthy controls. The association between rs2221903A/G and rs2055979G/T of the IL-21 gene and the risk of HCC and metastasis, as well as the clinico-pathological features, were analyzed. While rs2221903A/G polymorphism was not polymorphic in our cohort, patients carrying the genotype TT and allele T of the rs2055979G/T polymorphism had a significantly lower risk of HCC when comparing with HCC group and healthy controls. Also, participants carrying the aforementioned genotype and allele had a significantly lower risk of metastasis when comparing metastatic group with both nonmetastatic group and control group. The rs2055979G/T polymorphism was not significantly associated with clinico-pathological features of HCC. This is the first study to report a relationship between an intronic polymorphism in IL-21 gene and HCC and metastasis risk in the Egyptian people, in addition to identifying a potential new marker for the early detection and treatment of HCC.     

Association between two single nucleotide polymorphisms at corresponding microRNA and schizophrenia in a Chinese population

Numerous linkage and association studies have been performed to identify genetic predispositions to schizophrenic (SCZ) in different populations, but its genetic basis remains unclear. Some findings may provide a clue in understanding the association between abnormal immunity and SCZ. MicroRNA (miRNA) involves in regulating both schizophrenic and immunity as previous reported. And single nucleotide polymorphisms (SNPs) within miRNAs can change their characteristics, resulting in functional and/or phenotypic changes. So two SNPs (hsa-pre-mir-146a rs2910164 G>C and hsa-mir-499 rs3746444 T>C) at two miRNAs, were genotyped to demonstrate their association with susceptibility to SCZ. Polymorphisms were analyzed among 268 Chinese schizophrenic patients and 232 healthy controls by PCR-RFLP and validated by sequencing. No association was found between the two polymorphisms and SCZ either in cases or in controls. SCZ patients with family history showed significant increase of the G allele frequency of rs2910164 in comparison to those without (P = 0.018). The CC genotype frequency of rs3746444 was also higher in the patients having hallucinations than those without hallucinations (P = 0.012). In addition, patients carrying CC genotype of rs3746444 were more likely to be lack of motivation in comparison to normal controls (P = 0.042). Allele and genotype frequency of rs2910164 showed no significant difference between patients and normal subjects or between patients with and without clinical variables. Although patients carrying CC genotype of rs3746444 were found to be more likely to develop hallucination and individuals carrying C allele to lack motivation, there is lacking association between SCZ and the two SNPs at miRNAs, which may regulate immune response.     

Leptin −2548 G/A polymorphisms are associated to clinical progression of oral cancer and sensitive to oral tumorization in nonsmoking population

Oral cancer is causally associated with environmental carcinogens, and the susceptibility to carcinogen-mediated tumorigenesis is proposed to be genotype-dependent. Leptin (LEP) and leptin receptor (LEPR) both play a crucial role in the mediation of physiological reactions and carcinogenesis and may serve as a candidate biomarker of oral cancer. The current case-control study aimed to examine the effects of LEP −2548 G/A (rs7799039), LEPR K109R (rs1137100), and LEPR Q223R (rs1137101) single-nucleotide polymorphisms (SNPs) with or without interacting to environmental carcinogens on the risk for oral squamous cell carcinoma. The SNPs of three genetic allele, from 567 patients with oral cancer and 560 healthy controls in Taiwan were analyzed. The results shown that the patients with polymorphic allele of LEP −2548 have a significant low risk for the development of clinical stage (A/G: adjusted odds ratio [AOR] = 0.670, 95% confidence interval [CI] = 0.454-0.988, P < 0.05; A/G + G/G: AOR = 0.676, 95% CI = 0.467-0.978, P < 0.05) compared to patients with ancestral homozygous A/A genotype. In addition, an interesting result was found that the impact of LEP −2548 G/A SNP on oral carcinogenesis in subjects without tobacco consumption is higher than subjects with tobacco consumption. These results suggest that the genetic polymorphism of LEP −2548 G/A (rs7799039), LEPR K109R (rs1137100), and LEPR Q223R (rs1137101) were not associated to the susceptibility of oral cancer; SNP in LEP −2548 G/A showed a poor clinicopathological development of oral cancer; population without tobacco consumption and with polymorphic LEP −2548 G/A gene may significantly increase the risk to have oral cancer.     

A Panel of Serum Biomarkers Differentiates IgA Nephropathy from Other Renal Diseases

Background and Objectives

There is increasing evidence that galactose-deficient IgA1 (Gd-IgA1) and Gd-IgA1-containing immune complexes are important for the pathogenesis of IgA nephropathy (IgAN). In the present study, we assessed a novel noninvasive multi-biomarker approach in the diagnostic test for IgAN.

Materials and Methods

We compared serum levels of IgA, IgG, Gd-IgA1, Gd-IgA1-specific IgG and Gd-IgA1-specific IgA in 135 IgAN patients, 79 patients with non-IgAN chronic kidney disease (CKD) controls and 106 healthy controls. Serum was collected at the time of kidney biopsy from all IgAN and CKD patients.

Results

Each serum marker was significantly elevated in IgAN patients compared to CKD (P<0.001) and healthy controls (P<0.001). While 41% of IgAN patients had elevated serum Gd-IgA1 levels, 91% of these patients exhibited Gd-IgA1-specific IgG levels above the 90th percentile for healthy controls (sensitivity 89%, specificity 92%). Although up to 25% of CKD controls, particularly those with immune-mediated glomerular diseases including lupus nephritis, also had elevated serum levels of Gd-IgA1-specific IgG, most IgAN patients had elevated levels of Gd-IgA1-specific antibody of both isotypes. Serum levels of Gd-IgA1-specific IgG were associated with renal histological grading. Furthermore, there was a trend toward higher serum levels of Gd-IgA1-specific IgG in IgAN patients with at least moderate proteinuria (≥1.0 g/g), compared to patients with less proteinuria.

Conclusions

Serum levels of Gd-IgA1-specific antibodies are elevated in most IgAN patients, and their assessment, together with serum levels of Gd-IgA1, improves the specificity of the assays. Our observations suggest that a panel of serum biomarkers may be helpful in differentiating IgAN from other glomerular diseases.