Antibody Positive Subgroup Research Articles

Non-infectious uveitis referred forpediatric rheumatologic assessment andmanagement: A Portuguese retrospective study.

Pediatric uveitis poses challenges in diagnosis and treatment due to asymptomatic or oligosymptomatic presentations and high rates of intraocular complications. This study aimed to characterize clinical manifestations and treatment approaches of pediatric uveitis patients in a northern Portuguese tertiary hospital. A retrospective study was conducted involving 41 patients diagnosed with uveitis between 2006 and 2021. All individuals identified by the Opthalmology department were referred to Pediatric Rheumatology outpatient clinic. Demographic, clinical, treatment, and intraocular complications data were collected. Of the patients, 78% had anterior uveitis, 17% had panuveitis, and 5% had intermediate uveitis. Uveitis associated with juvenile idiopathic arthritis (JIA) was the most common cause (43.9%), predominantly in the oligoarticular, anti-nuclear antibody-positive subgroup. Complications were identified in 80.5% of the patients. Uveitis associated with JIA was diagnosed earlier [5.0 years (3.0-10.5) vs. 9.0 years (5.5-14.0), P = .036], more frequently in asymptomatic patients (71% vs. 23%, P = .010), had a more insidious installation (71% vs. 17%, P = .004), and required more tumor necrosis factor (TNF) inhibitor treatment (70% vs. 39%, P = .027). The high rates of intraocular complications and systemic pathology association highlight the need for a combined approach of ophthalmology and pediatric rheumatology in the diagnosis and treatment of pediatric uveitis.

Optimal validation of accuracy in antibody assays and reasonable definition of antibody positive/negative subgroups in neuroimmune diseases: a narrative review.

In neuroimmune diseases, autoantibodies are not only used for diagnosis, but also as markers for assessing disease severity and treatment efficacy, and as variables in predicting the prognosis and in subgroup classification. Accuracy of an assay is a prerequisite for using antibodies in the diagnosis and management. The antibody positive subgroup is important in constellating phenotypes, while the antibody negative subgroup provides an opportunity for discovery of new antibodies. This review is to discuss the validation studies of diagnostic accuracy in antibody assays and reasonable definitions of antibody positive/negative subgroups in neuroimmune diseases. The literature discussing validation studies of diagnostic accuracy in antibody assays and reasonable definition of antibody positive/negative subgroups in autoimmune diseases was broadly searched and discussed. The designs of a validation study, principles in defining the disease spectrum and biases, interpretation of the testing result and specific considerations for validation studies in neuroimmune diseases (such as phenotypes and inclusion criteria, control group selection, dynamic changes of antibody composition and sampling time, relationship between duration and severity of disease and antibody status, and pre-test factor), and improvement of antibody test techniques, as well as definitions and algorithms in defining antibody positive/negative subgroups in clinical practice and researches, are discussed. The successful implementation of validation studies of autoantibody assays in neuroimmune diseases depends on reasonable design, phenotypic profiles of included patients and potential inclusion bias, test result interpretation and the influence from inclusion criteria, control group selection, patient characteristics on specimen sampling and pre-test factors. Reasonable definitions on antibody positive/negative groups may be different in clinical practice and researches, and rigorous definitions are conducive to constellation of disease phenotype and the exploration of new antibodies within a disease entity.

Epidemic characteristics of pathogen spectrum and cerebrospinal fluid analysis of severe hand, foot, and mouth disease in Hangzhou, 2016

Objective To investigate the etiology composition of enterovirus (EV) in patients with severe hand, foot, and mouth disease (HFMD) in children. To assess the diagnostic value of cerebrospinal fluid (CSF) tests in severe HFMD, and to find the key laboratory tests for severe HFMD. Methods A total of 288 hospitalized cases of children clinically diagnosed with severe HFMD in Hangzhou Children′s Hospital were included from March to July 2016. Throat swabs were collected and enterovirus nucleic acids were detected by fluorescence quantitative reverse transcription (RT)-PCR. Synchronous CSF and serum samples were collected for EV-A71 and CV-sackievirus A16 (CV-A16)-IgM antibody detection. CSF samples underwent routine and biochemical tests. Normally distributed continuous variables were compared using t test. Non-normal distribution continuous variables were compared using Mann-Whitney U test. Differences between categorical variables were compared with χ2 test. Results The total positive rate of enterovirus nucleic acid EV-A71/CV-A16/EV by fluorescence quantitative RT-PCR in the 288 cases of children clinically diagnosed with HFMD was 83.7% (241/288), including EV-A71 55.2% (159/288), CV-A16 4.9% (14/288) and the other enterovirus 23.6% (68/288). Among the other enterovirus group, there were 29.4% CV-A6 (20/68) , 16.2% CV-A4 (11/68) and CV-A10 10.3% (7/68). The total positive rate of combined serum and CSF detection of EV nucleic acid and EV-A71 and CV-A16 IgM antibody was 98.3% (283/288). EV nucleic acid positive rate was 83.7% (24/288). The positive rates were statistically different (χ2 =37.289, P=0.000). The CSF nucleated cells count in EV-A71 positive subgroup was higher than those in CV-A16 positive subgroup and other enteroviruses subgroup (Z=-4.472 and -9.991, respectively, both P 400 mg/L) rate in EV-A71 positive subgroup was higher than those in CV-A16 positive subgroup and other enteroviruses subgroup (χ2=4.956 and 11.795, respectively, both P<0.05). The CSF nucleated cell counts and positive rates in EV-A71 IgM antibody-positive subgroup were both higher than those in antibody-negative subgroup (both P<0.05). The CSF protein level and elevated proportion in antibody-positive subgroup were both higher than those in antibody-negative subgroup (both P<0.05). The lactate dehydrogenase concentration in antibody-positive subgroup was significantly higher than those in antibody-negative subgroup (P<0.05). The EV-A71 IgM antibody in serum was significantly correlated with the antibody in CSF (r=0.600, P<0.05). Conclusions EV-A71 is still the most important pathogen of severe HFMD in Hangzhou in 2016. Other enterovirus such as CV-A6, CV-A4 increases compared to those in 2014 and 2015. The CSF routine and biochemical tests and the IgM antibody levels can serve as an important indicator for the diagnosis of children with severe HFMD. Key words: Hand, foot and mouth disease; Antibodies; Cerebrospinal fluid

Detection of cerebrospinal fluid anti-enterovirus 71 IgM in children with severe hand, food and mouth disease induced by enterovirus 71 infection and its clinical significance

To detect the anti-enterovirus 71 (EV71) IgM level in cerebrospinal fluid (CSF) of children with severe hand, foot and mouth disease (HFMD) induced by EV71 and then analyze the relationships among the IgM antibody levels, CSF routine examination and patients' clinical features, and thus to evaluate the clinical significance of anti-EV71 IgM as a new indicator for early diagnosis of children with severe HFMD induced by EV71. A total of 294 laboratory-confirmed cases of children with severe HFMD infected with EV71 were enrolled into the research group from March 2014 to June 2014, consisting of 53 fatal cases and 241 severe cases, and their CSF samples underwent enzyme-linked immunosorbent assay (ELISA) for anti-EV71 IgM levels, CSF routine and biochemical tests. Forty-one cases of children with severe HFMD induced by other enteroviruses were collected as antibody-testing control group during the same period. In the research group, the total positive rate of anti-EV71 IgM in 294 CSF samples of children with severe HFMD infected by EV71 was 60.2% (177/294); the positive rate of anti-EV71 IgM in the fatal HFMD subgroup was 62.3% (33/53); the positive rate of anti-EV71 IgM in the severe HFMD subgroup was 59.8% (144/241). In the control group, the results of CSF anti-EV71 IgM tests were all negative (0/41). In the research group, patients in antibody-positive subgroup (2.5±1.2) years old were younger than those in antibody-negative subgroup (2.9±1.1) years old (t=2.595, P=0.010). And within the antibody-positive subgroup, the patients ((1.9±0.7) years old) with fatal type disease were younger than those ((2.6±1.2) years old) with severe type disease (t=3.150, P=0.002). The CSF nucleated cells count and positive rates (105 (56,180) ×10(6) /L; 97.7% (173/177)) in antibody-positive subgroup were higher than those (62(30,150) ×10(6) /L; 83.8% (98/117)) in antibody-negative subgroup (Z=3.663, P=0.000; χ(2)=19.089, P=0.000). In antibody-positive subgroup, the percentage of monocytes (57±25)% was higher than that of polykaryocytes (43±25)%. In antibody-negative subgroup, the percentage of monocytes (50±26)% was close to that of polykaryocytes (50±26)%. In the antibody-positive subgroup, the ratio of the patients with nucleated cells count higher than 100×10(6)/L in fatal type group and severe type group was 69.7% (23/33) and 47.2% (68/144) respectively (χ(2)=5.429, P=0.02). The CSF protein quantity and positive rates in antibody-positive subgroup were higher than those in antibody-negative subgroup (Z=2.158, P=0.031; χ(2)=5.921, P=0.015). The anti-EV71 IgM levels in CSF can serve as an important indicator for early diagnosis of children with severe HFMD induced by EV71. And the anti-EV71 IgM levels in CSF correlated to the CSF nucleated cells count and classification and CSF protein quantity. In the antibody-positive subgroup, the higher the nucleated cell count or the younger the age, the higher the possibility of patients to develop into fatal cases.

Brief Report: Anti–Carbamylated Protein Antibodies Are Present in Arthralgia Patients and Predict the Development of Rheumatoid Arthritis

AbstractObjectiveRecently, we discovered a new autoantibody system in rheumatoid arthritis (RA): anti–carbamylated protein (anti‐CarP) antibodies. These antibodies have value in predicting joint destruction; however, it is not clear whether they are present before the diagnosis of RA and whether they have value as predictors of RA development. Therefore, we studied whether anti‐CarP antibodies are present in patients with arthralgia and whether their presence is associated with the development of RA.MethodsSera from 340 arthralgia patients who did not have clinical signs of arthritis but who were positive for IgM rheumatoid factor (IgM‐RF) and/or anti–cyclic citrullinated peptide 2 (anti–CCP‐2) and 32 healthy controls were tested for anti‐CarP IgG antibodies. Of the patients with arthralgia, 111 were IgM‐RF positive/anti–CCP‐2 antibody negative and 229 were anti–CCP‐2 antibody positive. Patients were observed for the development of RA (based on the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria) during a median followup period of 36 months. Cox proportional hazards regression analysis was performed to compare the risk of developing RA between arthralgia patients who were positive for anti‐CarP antibodies and those who were negative for anti‐CarP antibodies during followup.ResultsAnti‐CarP antibodies were present in the sera of 39% of the patients. One hundred twenty patients developed RA, after a median of 12 months (interquartile range [IQR] 6–24). The presence of anti‐CarP antibodies was associated with the development of RA in the entire arthralgia cohort after correction for RF and anti–CCP‐2 antibody status (hazard ratio 1.56 [95% confidence interval 1.06–2.29], P = 0.023), as well as in the anti–CCP‐2 antibody–positive subgroup (odds ratio 2.231 [95% confidence interval 1.31–3.79], P = 0.003).ConclusionAnti‐CarP antibodies are present in patients with arthralgia, and their presence predicts the development of RA independent of anti–CCP‐2 antibodies.

Particular association of clinical and genetic features with autoimmunity to citrullinated α-enolase in rheumatoid arthritis

To confirm that the presence of anti-citrullinated α-enolase peptide 1 (anti-CEP-1) antibodies identifies a subgroup of patients with rheumatoid arthritis (RA). DNA and serum samples were obtained from 451 patients with RA and 279 healthy control subjects, all of whom were of Spanish ancestry. Antibodies to cyclic citrullinated peptide (CCP) and CEP-1 were measured by enzyme-linked immunosorbent assay. HLA-DRB1 and the R620W single-nucleotide polymorphism of PTPN22 were genotyped. Anti-CEP-1 and anti-CCP antibodies were observed in 26.8% and 71.2% of the patients with RA, respectively. Most of the patients (86.6%) with anti-CEP-1 antibodies also had anti-CCP antibodies. Erosive arthritis, rheumatoid factor (RF) positivity, and the presence of the HLA shared epitope (especially the DRB1*04 alleles) were disproportionately associated with the group of patients with both antibodies. In addition, evidence of a significant interaction between the shared epitope and the risk allele of PTPN22 was observed only in these patients. In contrast, the association with these clinical and genetic features was weaker in patients with anti-CCP antibodies but lacking anti-CEP-1 antibodies. These results were obtained in patients in whom the prevalence of RA risk factors differed from that in other previously studied patients. We observed that autoimmunity against citrullinated α-enolase may identify a subset of patients with a higher frequency of joint erosions and RF positivity. In addition, we confirmed the disproportionately large effect of the susceptibility alleles of HLA-DRB1 and their interaction with PTPN22 in this subset of patients. These results extend, confirm, and generalize the evidence supporting the specificity of the anti-CEP-1 antibody-positive subgroup of patients with RA among anti-CCP antibody-positive patients with RA.

Molecularly defined HLA-DR2 alleles in ulcerative colitis and an antineutrophil cytoplasmic antibody-positive subgroup

Background/Aims: Although HLA-DR2 is associated with Japanese ulcerative colitis, data regarding an HLA-DR2 association in other populations are conflicting. A recent study suggests that HLA-DR2 is only associated with antineutrophil cytoplasmic antibody-positive ulcerative colitis. The aim of this study was to determine whether HLA-DR2 or the molecularly defined alleles within the HLA-DR2 group are associated with ulcerative colitis or a perinuclear antineutrophil cytoplasmic antibody-positive subgroup. Methods: Unrelated white patients with a history of ulcerative colitis (n = 97) and control subjects matched to patients for Jewish ethnicity and sex (n = 149) were studied. An immunofluorescence assay was used to detect perinuclear antineutrophil cytoplasmic antibodies. A molecular, DNA-based method was used to perform HLA-DR2 typing. Results: HLA-DRB1 ∗1601 was present in 11 of 149 controls and 1 of 97 patients ( P = 0.031, corrected P, not significant; Fisher's Exact Test). There were no other significant differences between ulcerative colitis or ulcerative colitis stratified by perinuclear antineutrophil cytoplasmic antibody status and controls. Conclusions: The HLA-DR2 group of alleles is not associated with ulcerative colitis or a perinuclear antineutrophil cytoplasmic antibody-positive subgroup. The unexpected finding of a decreased frequency of HLA-DRB1 ∗1601 in ulcerative colitis should be further investigated.