Rheumatoid Factor Test Research Articles

HLA-DRB1*01 predicts treatment outcome in juvenile idiopathic arthritis: A retrospective-prospective cohort study.

Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory autoimmune disease in childhood, significantly contributing to both short- and long-term disability. While certain human leukocyte antigen (HLA) class II alleles are known to be associated with specific subgroups of JIA, emerging evidence suggests a strong correlation between these alleles and treatment response. This study involved 143 JIA patients diagnosed according to International League of Associations for Rheumatology criteria. Each patient underwent HLA class II typing, including HLA-B27, as well as tests for rheumatoid factor (RF) and antinuclear antibodies (ANA). Comprehensive rheumatological assessments were conducted at diagnosis, with follow-ups at three and six months post-onset. After six months of methotrexate (MTX) treatment, patients were categorized as responders or non-responders. Responders achieved clinically inactive disease based on the American College of Rheumatology Provisional Criteria for Defining Clinical Inactive Disease and Clinical Remission. Non-responders, who did not reach clinically inactive disease after six months of treatment, required the addition of another non-biological disease-modifying antirheumatic drug (DMARD) or a biological DMARD. Our analysis revealed that the HLA-DRB1*01 allele is a significant prognostic marker for therapeutic response, predicting therapeutic resistance (P=0.01). The most prevalent HLA-DRB1 alleles in the treatment-resistant group were HLA-DRB1*08:11 (11.3%), HLA-DRB1*01:01 (8.5%), HLA-DRB1*01:13, HLA-DRB1*04:11 (7%), HLA-DRB1*08:13, and HLA-DRB1*08:15 (4.2%). These findings highlight the critical role of HLA class II alleles in pediatric rheumatology, particularly in relation to treatment response and disease prognosis. In the era of personalized medicine, understanding the genetic contributions to treatment response and outcomes in JIA patients is essential. A key limitation of this study was the lack of comparison of treatment responses across different JIA subtypes. Future studies should prioritize evaluating MTX efficacy within specific JIA subgroups to enable a more tailored understanding of its effectiveness.

COEXISTENCE OF GOLDENHAR SYNDROME WITH JUVENILE IDIOPATHIC ARTHRITIS: A CAUSAL LINK OR MERE COINCIDENCE?

Goldenhar syndrome, a rare congenital anomaly primarily affecting the face, external ear and vertebrae, and juvenile idiopathic arthritis (JIA), a chronic inflammatory disease in children under 16, represent distinct and uncommon clinical entities. We report the case of a five-and-a-half-year-old girl, with a history of treated congenital hip dislocation, admitted for persistent joint pain for over 6 months, affecting both knees, wrists and ankles with inflammatory signs without associated visceral manifestations. Clinical examination revealed a dysmorphic facies characteristic of Goldenhar syndrome, including facial asymmetry with mandibular hypoplasia, auricular anomalies such as a bilateral pre-tracheal appendix, an acrochordon on the right cheek, a pre-auricular sinus, microtia, and a closed right external auditory canal. A lumbar scoliosis was also identified on dorsolumbar spine imaging, with a CT scan of the rock that objectified an imperforation of the right external auditory canal and lack of visualization of the tympanic membrane, consolidating the diagnosis of Goldenhar syndrome.Biologically, the patient presented with inflammatory anemia with a moderate inflammatory syndrome, as well as hypergammaglobulinemia detected by protein electrophoresis. Tests for antinuclear antibodies and rheumatoid factor were negative (15 IU/mL). X-rays of the affected joints were taken, and the diagnosis of Idiopathic Juvenile Arthritis was retained after eliminating all differential diagnoses. This unusual coexistence raises complex diagnostic and therapeutic challenges, requiring a multidisciplinary approach and ongoing surveillance for comprehensive management.

Rapid identification of inflammatory arthritis and associated adverse events following immune checkpoint therapy: a machine learning approach.

Immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA) poses a major clinical challenge to ICI therapy for cancer, with 13% of cases halting ICI therapy and ICI-IA being difficult to identify for timely referral to a rheumatologist. The objective of this study was to rapidly identify ICI-IA patients in clinical data and assess associated immune-related adverse events (irAEs) and risk factors. We conducted a retrospective study of the electronic health records (EHRs) of 89 patients who developed ICI-IA out of 2451 cancer patients who received ICI therapy at Northwestern University between March 2011 to January 2021. Logistic regression and random forest machine learning models were trained on all EHR diagnoses, labs, medications, and procedures to identify ICI-IA patients and EHR codes indicating ICI-IA. Multivariate logistic regression was then used to test associations between ICI-IA and cancer type, ICI regimen, and comorbid irAEs. Logistic regression and random forest models identified ICI-IA patients with accuracies of 0.79 and 0.80, respectively. Key EHR features from the random forest model included ICI-IA relevant features (joint pain, steroid prescription, rheumatoid factor tests) and features suggesting comorbid irAEs (thyroid function tests, pruritus, triamcinolone prescription). Compared to 871 adjudicated ICI patients who did not develop arthritis, ICI-IA patients had higher odds of developing cutaneous (odds ratio [OR]=2.66; 95% Confidence Interval [CI] 1.63-4.35), endocrine (OR=2.09; 95% CI 1.15-3.80), or gastrointestinal (OR=2.88; 95% CI 1.76-4.72) irAEs adjusting for demographics, cancer type, and ICI regimen. Melanoma (OR=1.99; 95% CI 1.08-3.65) and renal cell carcinoma (OR=2.03; 95% CI 1.06-3.84) patients were more likely to develop ICI-IA compared to lung cancer patients. Patients on nivolumab+ipilimumab were more likely to develop ICI-IA compared to patients on pembrolizumab (OR=1.86; 95% CI 1.01-3.43). Our machine learning models rapidly identified patients with ICI-IA in EHR data and elucidated clinical features indicative of comorbid irAEs. Patients with ICI-IA were significantly more likely to also develop cutaneous, endocrine, and gastrointestinal irAEs during their clinical course compared to ICI therapy patients without ICI-IA.

Prediction of Sjögren’s disease diagnosis using matched electronic dental-health record data

BackgroundSjögren’s disease (SD) is an autoimmune disease that is difficult to diagnose early due to its wide spectrum of clinical symptoms and overlap with other autoimmune diseases. SD potentially presents through early oral manifestations prior to showing symptoms of clinically significant dry eyes or dry mouth. We examined the feasibility of utilizing a linked electronic dental record (EDR) and electronic health record (EHR) dataset to identify factors that could be used to improve early diagnosis prediction of SD in a matched case-control study population.MethodsEHR data, including demographics, medical diagnoses, medication history, serological test history, and clinical notes, were retrieved from the Indiana Network for Patient Care database and dental procedure data were retrieved from the Indiana University School of Dentistry EDR. We examined EHR and EDR history in the three years prior to SD diagnosis for SD cases and the corresponding period in matched non-SD controls. Two conditional logistic regression (CLR) models were built using Least Absolute Shrinkage and Selection Operator regression. One used only EHR data and the other used both EHR and EDR data. The ability of these models to predict SD diagnosis was assessed using a concordance index designed for CLR.ResultsWe identified a sample population of 129 cases and 371 controls with linked EDR-EHR data. EHR factors associated with an increased risk of SD diagnosis were the usage of lubricating throat drugs with an odds ratio (OR) of 14.97 (2.70-83.06), dry mouth (OR = 6.19, 2.14–17.89), pain in joints (OR = 2.54, 1.34–4.76), tear film insufficiency (OR = 27.04, 5.37–136.), and rheumatoid factor testing (OR = 6.97, 1.94–25.12). The addition of EDR data slightly improved model concordance compared to the EHR only model (0.834 versus 0.811). Surgical dental procedures (OR = 2.33, 1.14–4.78) were found to be associated with an increased risk of SD diagnosis while dental diagnostic procedures (OR = 0.45, 0.20–1.01) were associated with decreased risk.ConclusionUtilizing EDR data alongside EHR data has the potential to improve prediction models for SD. This could improve the early diagnosis of SD, which is beneficial to slowing or preventing complications of SD.

Safflower extract (Carthamus tinctorius Linn.) suppresses proinflammatory cytokines level in rheumatoid arthritis mice model stimulated by complete Freund’s adjuvants

Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation of the synovial membrane, and swelling, associated with excessive production of proinflammatory cytokines. In addition, anti-citrullinated protein antibodies is excessively high in RA. Carthamus tinctorius Linn. (C. tinctorius), commonly known as Safflower, is widely used as traditional medicine in Indonesia and has anti-inflammatory properties. This study aims to determine cell viability on HEK293 cells and the anti-RA activity of the ethanol extract of C. tinctorius on reducing edema in animal models of RA mice and to determine the anti-RA activity ethanol extract C. tinctorius against rheumatoid factor (RF) in RA mice. In this study, HEK293 cell line was treated with C. tinctorius extract at various concentrations. In addition, mice’s paws were examined after being injected with complete Freund’s adjuvant (CFA) as an intraplantar RA inducer and treated with 2.5 mg/kg body weight (BW) of methotrexate, and extract C. tinctorius at various concentrations orally once a day for 14 days. Then, the paw’s thickness was measured using a gauge meter, arthritis index scoring was observed daily, and agglutination in the RF test was observed on the 17th and 31st days. The collected data was analyzed using one-way analysis of variance. Moreover, an In-Silico test was carried out by measuring the affinity and stability of C.tintorius extract as an anti-RA agent against the cytokines IL-1β and tumor necrosis factor-alpha. The test results showed C. tinctorius at various concentrations were safe to HEK293 cell lines and the administration of C. tintorius extract at 100, 200, and 400 mg/kg BW doses could reduce paw thickness, arthritis index scoring >1, and no agglutination occurred in the RF test. It can concluded that the C. tintorius extract is safe to HEK293 and has activity against CFA-induced RA.

Double positivity for rheumatoid factor and anti-CCP autoantibodies: improving referral from primary care of patients suspected of having rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic progressive autoimmune inflammatory disease with significant morbidity and mortality. The course of the disease can be modified if diagnosis is early and treatment appropriate. In this study, we aimed to evaluate a new strategy for early identification of RA patients in primary care settings (the 'diagnostic bottleneck') based on serological biomarkers and to manage inappropriate rheumatoid factor (RF) laboratory test requests. A two-arm study was carried out. The first arm corresponded to a retrospective observational descriptive study of patients referred for RF testing from primary care using the current laboratory workflow. The second arm included the following prospective interventions: cancelation of RF requests corresponding to patients with previous negative results for RF over a one-year period; and automatic reflex testing antibodies against cyclic citrullinated proteins (anti-CCP) for patients displaying RF values >30IU/ml. Outcomes from both arms were then compared. As double positivity for RF and anti-CCP notably increases the positive likelihood ratio of RA. The intervention enabled a reduction of 2813 tests in 22 months. Moreover, the frequency of unnecessary referrals was reduced from 22% to 8.2%, while that of missed patients decreased slightly (from 21% to 16%), with the number of patients diagnosed per RF request remaining unchanged. In terms of costs, we saved 19.4 RF tests per anti-CCP test added.We developed a simple and cost-effective strategy for reducing the time to diagnosis of RA that can improve patients' quality of life. This approach was supported by primary and specialised care.

The MIDORA trial: a phase II, randomised, double-blind, placebo-controlled, mechanistic insight and dosage optimisation study of the efficacy and safety of dazodalibep in patients with rheumatoid arthritis

ObjectivesTo evaluate the safety, efficacy and response duration of four different dosing regimens of dazodalibep (DAZ), a non-antibody biological antagonist of CD40L, in patients with rheumatoid arthritis (RA).MethodsThis double-blind study...

Case 316: Progressive Pseudorheumatoid Dysplasia.

A 10-year-old North Indian boy presented with swelling of multiple joints in his hands for the past 3 years. This swelling involved the small joints of his hands and some restriction of joint movement, without any associated tenderness or morning stiffness. No other joints were symptomatically involved. Prior to visiting our hospital, he had received disease-modifying antirheumatoid drugs for suspected juvenile idiopathic arthritis, without any clinical benefit. On examination, the metacarpophalangeal and interphalangeal joints were nontender but had swelling and flexion deformities. He also had a short stature (below the third centile) for his age. Inflammatory markers, including erythrocyte sedimentation rate (7 mm per hour; normal range, 0-22 mm per hour) and C-reactive protein level (1.5 mg/L; normal level, <10 mg/L), were normal, and the rheumatoid factor test result was negative. A skeletal survey of the patient was performed.

P196 ENDOCARDITIS MASQUERADING AS STILL‘S DISEASE: WHEN AN ECHOCARDIOGRAM SAVES YOUR LIFE

Abstract A 44–year–old man in apparent good health thus far presented with weight loss and fever preceded by shivers, profuse sweating, and arthralgias. Blood tests documented normal white blood count with slightly altered CRP and ESR. Chest X–rays did not find pleuro– parenchymal lesions with normal cardiac silhouette. Abdomen ultrasounds was regular. Due to the persistence of the symptoms, he was referred to a rheumatologist who diagnosed Adult Still’s disease (AOSD) and recommended therapy with prednisone and sulfasalazine, interleukin–1 inhibitor, with the resolution of the fever. After three months, because of the recrudescence of the fever, he was admitted to the emergency room a total–body CT–scan documented inflammatory–abscess lesions in the brain and hypodense areas in the spleen. ECG showed type 1 second–degree atrioventricular (AV) block. The patient was therefore transferred to the Cardiology Department; echocardiograms documented an endocardic mass on the aortic valve and suspected periannular abscess also infiltrating the interventricular septum. The patient underwent urgent surgery with excision of the aortic valve, opening and draining of the abscessual cavities, reconstruction of the aortic annulus with bovine pericardium patch and aortic valve replacement with bioprosthesis. The patient did not present further febrile episodes after surgery but a pacemaker implantation was necessary due to persistent AV block. Biological material sent for culture was positive for S. gallolyticus. AOSD is one of the most common conditions responsible for fevers of unknown origin. It is characterized by fever, arthritis, evanescent rash, leukocytosis, and multiorgan involvement. Yamaguchi criteria required for the diagnosis of AOSD are as follows: main criteria: Fever &amp;gt;39°C, lasting 1 week or more, Arthralgia or arthritis, lasting 2 weeks or more, Typical rash, Leukocytosis &amp;gt;10,000/mm3; Minor criteria: Sore throat, Recent development of significant lymphadenopathy, Hepatomegaly or splenomegaly, Negative tests for antinuclear antibodies and rheumatoid factor; Exclusion criteria: Infections, Malignancies, Other rheumatic diseases.

E030 Rheumatologists beware! Digital ischaemia as a presenting feature in metastatic ovarian cancer

Abstract Background/Aims Digital ischaemia is an umbrella term to describe the spectrum of acral vascular phenomena irrespective of aetiology, ranging from temporary (as in Raynaud’s phenomenon) to permanent (necrosis). It can be the presenting feature in multiple cancer types, and can be present with or without other features of connective tissue disease. Methods A 54-year-old woman was referred to Rheumatology with a four-day history of acute pain and ischaemic discolouration of all her fingertips bilaterally. There was no history of Raynaud’s phenomenon and no other clinical features of connective tissue disease. She had never smoked. There was a family history of breast cancer in her maternal aunt. She was admitted under vascular surgery for urgent review. All ten fingertips were ischaemic, with a capillary refill time of greater than five seconds. The history was otherwise significant for abdominal bloating, altered bowel habit and fatigue. Examination revealed normal peripheral pulses with no bruits, normal heart sounds and chest sounds. Her abdomen was soft with a mildly enlarged liver. Results FBC, U&amp;E, and LFTs showed no abnormalities. CRP, ESR, ANA, serum protein electrophoresis and complement levels were all normal. Blood tests for ANCA, rheumatoid factor and anti-CCP were also negative. Lupus anticoagulant, anti-cardiolipin and anti-B2-glycoprotein were all negative. The tumour marker CA125 was markedly elevated at 837kU/L (0.0-35.0kU/L). A CT abdomen &amp; pelvis showed a large right-sided adnexal mass with multiple enhancing peritoneal and omental nodules and moderate ascites. Biopsy of a metastatic deposit in the omentum revealed high grade serous ovarian adenocarcinoma. Partial improvement in digital ischaemia was achieved with iloprost and maintenance apixaban and sildenafil. Four cycles of carboplatin and paclitaxel chemotherapy produced near-complete resolution of digital ischaemia symptoms, corresponding to a fall in her CA125 level and reduction in the size of the ovarian mass and intra-abdominal metastases on CT. Ten cases of digital ischaemia associated with ovarian cancer have been described prior to this. The age of onset ranged from 45 to 71, with a median age of 56. Most patients had digital ischaemia without features of connective tissue disease. Four had no blood test abnormalities other than a raised tumour marker CA125. The time from onset of digital ischaemia to diagnosis of ovarian cancer ranged from less than one week to 2 years, with a median time of four months. Conclusion This case study supports previous findings that patients with digital ischaemia associated with ovarian cancer may have normal markers of inflammatory or rheumatological disease. Marked therapeutic responses can be achieved with systemic anti-cancer therapies. Therefore, underlying cancer should be suspected in patients with new-onset or worsening digital ischaemia over the age of 45. A high index of suspicion is required - rheumatologists beware! Disclosure J.H. Miller: None. P. Merry: None.

Case 316

A 10-year-old North Indian boy presented with swelling of multiple joints in his hands for the past 3 years. This swelling involved the small joints of his hands and some restriction of joint movement, without any associated tenderness or morning stiffness. No other joints were symptomatically involved. Prior to visiting our hospital, he had received disease-modifying antirheumatoid drugs for suspected juvenile idiopathic arthritis, without any clinical benefit. On examination, the metacarpophalangeal and interphalangeal joints were nontender but had swelling and flexion deformities. He also had a short stature (below the third centile) for his age. Inflammatory markers, including erythrocyte sedimentation rate (7 mm per hour; normal range, 0-22 mm per hour) and C-reactive protein level (1.5 mg/L; normal level, <10 mg/L), were normal, and the rheumatoid factor test result was negative. A skeletal survey of the patient was performed and is shown in Figures 1-6.

The assessment of rheumatoid factor levels and hemogram parameters as predictors for rheumatologic disease.

Many markers are used for clinical diagnosis in rheumatic diseases; rheumatoid factor (RF) is the most frequently used marker. However, RF is not specific to rheumatoid arthritis (RA). RF positivity is widely observed in patients with advanced age, infectious, autoimmune, and lymphoproliferative diseases. In this context, the objective of this study is to investigate the demographic characteristics, frequency of antinuclear antibody (ANA) and anti-cyclic citrullinated peptide (anti-CCP) positivity, hemogram parameters and distribution of the diagnoses in RF-positive patients followed at the rheumatology clinic. The population of this retrospective study consisted of patients above 18 years of age who were referred to have RF positivity by nephelometric method at Kahramanmaraş Necip Fazıl City Hospital Rheumatology Clinic between January 2020 and June 2022. The mean age of the 230 patients with a positive RF test result, 155 (76%) male and 55 (24%) female, was 52.7 ± 15.5 years. There were 81 (35.2%), 54 (23.5%), 73 (31.7%) and 22 (9.6%) patients with RF levels between 20 and 50 IU/mL, 50 and 100 IU/mL, 100 and 500 IU/mL, and above 500 IU/mL, respectively. There was no significant difference detected between the groups that were created based on the RF titers regarding demographic characteristics (P > 0.05). The rate of being diagnosed with any rheumatic disease was significantly lower in the group with RF levels between 20 and 50 IU/mL compared to other groups (P = 0.001). The distribution of rheumatic and non-rheumatic disease diagnoses according to RF levels did not reveal any significant difference between the groups (P = 0.369 and P = 0.147, respectively). RA was the most common (62.2%) rheumatic disease diagnosis among the patients included in the study. The leukocyte count was significantly higher in the group with RF levels above 500 IU/mL compared to the group with RF levels between 20 and 50 IU/mL (P = 0.024). There was no significant difference between the groups in other laboratory results, that is, hemogram, sedimentation, C-reactive protein, platelet, and lymphocyte/monocyte ratio (P > 0.05). The study findings indicate that RF positivity can be seen in the context of different rheumatological diseases; hence RF levels alone may not predict rheumatological disease. There was also no significant relationship between RF levels and ANA and anti-CCP positivity. The most common diagnosis in patients presenting with elevated RF levels was RA. Nevertheless, it should be noted that RF can be found asymptomatically in the general population.

Juvenile idiopathic arthritis-associated uveitis: the experience in Libya

Background: Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease. The development of associated uveitis represents a significant risk for serious complications, including permanent loss of vision. Initiation of early treatment is important for controlling JIA-uveitis, but the disease can appear asymptomatically, making frequent screening procedures necessary for patients at risk. As our understanding of pathogenic drivers is currently incomplete, it is difficult to assess which JIA patients are at risk of developing uveitis. In the present study, we described the prevalence and clinical profile of JIA-associated uveitis and out come among children in the Libyan clinical settings. Methods: A total of 90 JIA patients who fulfilled International League of Associations for Rheumatology (ILAR) diagnostic criteria were included in this retrospective study. The data collected were age, gender, age at disease onset and at diagnosis, and follow-up duration. Duration from JIA diagnosis to uveitis diagnosis. Antinuclear antibody (ANA), rheumatoid factor (RF), and human leukocyte antigen B-27 were evaluated for each patient. Results: A total of eight uveitis cases were identified among the 90 JIA cases, which gives a prevalence of 8.9%. All cases were females (100.0%), the majority were Libyans (87.5%), and their mean age was 12.3 (SD=4.3) years old. The mean age at JIA onset for this group was 5.3(SD=2.3) years old and that for JIA diagnosis 6.2 (SD=2.6) years old, with an average duration of JIA of 6.8 (SD=3.7) years. The most common JIA subtype in this group was oligoarthritis (50%), followed by poly arthritis (37.5%). The majority of the cases had a negative rheumatoid factor test (75%), and ANA was positive only in 1 of 7 valid cases (14.3%). Conclusion: Better recognition of uveitis in JIA is required to improve its outcome and avoid serious complications.

Management of simultaneous bilateral immune-mediated peripheral ulcerative keratitis.

Peripheral ulcerative keratitis (PUK) is a sight threatening disease, often immune mediated and can rapidly progress to corneal perforation. Here we report the successful management of simultaneous bilateral peripheral ulcerative keratitis presenting with corneal perforation with surgical intervention and systemic immunosuppression. A 41-year-old female presented with similarly located super-nasal peripheral ulcerative keratitis (PUK) in both eyes and focal area of adjoining scleritis in the left eye. Serological investigations for systemic immune-mediated conditions showed positive rheumatoid factor test. She underwent cyanoacrylate glue application in both eyes, and was started on topical and oral corticosteroids and oral immunomodulators, and the right eye stabilized. The left eye required a second surgical intervention with a corneal patch graft following which the condition stabilized. This case highlights the importance of investigating for an underlying systemic etiology in PUK and the role of systemic immunosuppression prior to and after surgical intervention in order to arrest the disease and prevent recurrences.

Sequential Tocilizumab and Tofacitinib Treatment for Systemic Juvenile Idiopathic Arthritis: a Case Report.

Systemic juvenile idiopathic arthritis (sJIA) is a complex and difficult to cure condition with high disability and mortality rates. Herein, we report the case of a patient with sJIA who was treated with sequential tocilizumab (TCZ) and tofacitinib treatment. The patient was a 4-year-old girl hospitalised with fever accompanied by multiple joint swelling and pain in June 2020. Laboratory tests revealed a white blood cell count of 15.3 × 109/L, platelet count of 676.8 × 109/L, haemoglobin of 91.8g/L, serum ferritin level of 1103.8U/L, erythrocyte sedimentation rate of 85.0mm/h, C-reactive protein level of 146.0g/L and interleukin (IL)-6 level of 288.0pg/ml. Rheumatoid factor and autoantibodies test results were negative, and she was diagnosed with sJIA. The patient was started on a combination of ibuprofen, methotrexate and TCZ, and her fever decreased to the normal range without any recurrence. Painful joint swelling had resolved significantly at 3-month follow-up. Janus kinase (JAK) inhibitors inhibit the effects of several cytokines, particularly IL-6, and are economical and convenient. Therefore, we selected tofacitinib to replace TCZ in this case, while the other drugs remained unchanged. Arthritis symptoms disappeared gradually after 9-month follow-up. In May 2021, the patient was hospitalised owing to a slight recurrence of the upper respiratory tract infection. She was administered one intravenous infusion of TCZ along with a switch to oral tofacitinib, which quickly relieved the symptoms. In March 2022, the patient's condition was stable. The curative effect of sequential TCZ and tofacitinib treatment was remarkable. IL-6 inhibitors sequential to JAK inhibitors could be a new option in the treatment of systemic juvenile idiopathic joints.

Serum protein electrophoresis and rheumatoid factor analysis is an effective screening strategy for cryoglobulinaemia

Accurate serum cryoglobulin detection is important to allow prompt treatment but laboratory testing requires stringent pre-analytical conditions and has long turnaround times. Serum protein electrophoresis (EPG) for paraproteinaemia and rheumatoid factor (RF) analysis may offer an effective initial screening strategy for the presence of cryoglobulinaemia. We retrospectively assessed the sensitivity of ancillary EPG and RF testing for the presence of serum cryoglobulinaemia in 586 eligible cryoglobulin positive samples received at the Royal Prince Alfred and Liverpool Hospital immunopathology laboratories over an 11-year period. Ninety-one percent of all cryoglobulin positive samples had either a detectable paraprotein or RF activity, with greatest sensitivity for type I and type II cryoglobulins (97% and 98%, respectively). The sensitivity remained high irrespective of whether EPG and RF analysis was performed with the same, or different, pre-analytical collection conditions to the cryoglobulin collection (92% vs 90%, p=0.46). Only two patients with detected cryoglobulins and no associated paraprotein or RF activity had clinical features of cryoglobulinaemia and neither required treatment. This study demonstrates that serum EPG and RF analysis has high sensitivity for the detection of clinically relevant cryoglobulinaemia, even when not collected under ideal pre-analytical conditions, and potentially offers a prompt and effective screening strategy.

Unexpected Detection of Anti-SARS-CoV-2 Antibodies Before the Declaration of the COVID-19 Pandemic.

Background:Limited information is currently available regarding the global incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections prior to the declaration of the coronavirus disease 2019 (COVID-19) pandemic, which may result in improper conclusions regarding the timing of viral transmission.MethodsWe investigated the presence of specific antibodies against the receptor-binding domain (RBD) of SARS-CoV-2 in archived serum samples that were collected from 478 healthy blood donors and patients in Madinah, Saudi Arabia, between October 2019 and January 2020. Enzyme-linked immunosorbent assay (ELISA) was performed to measure SARS-CoV-2 IgM and IgG antibodies. In addition, rheumatoid factor (RF) and urea dissociation tests were performed in all samples, which showed seropositivity for the SARS-CoV-2 IgM antibody. Additionally, Chemiluminescence immunoassays (CLIA) targeting the RBD of the SARS-CoV-2 spike (S) protein were performed to confirm the seropositivity of the samples.ResultsOverall, 20 (4.18%) serum samples were detected by ELISA to have SARS-CoV-2 IgG or IgM antibodies. Of these, 12 (2.51%) samples were positive for IgM antibody, and 8 (1.67%) were positive for IgG antibody. The 12 samples positive for SARS-CoV-2 IgM antibody were subjected to RF and urea dissociation tests, and all samples were RF-negative. The ELISA results were negative for 7 (58.33%) samples when subjected to urea dissociation prior to ELISA, whereas the other 5 (41.67%) samples remained positive. These 5 samples remained positive for the anti-S RBD IgG antibody in the CLIA. In addition, 3 of the 8 samples with IgG positivity according to the ELISA remained positive in the CLIA. After reviewing their data, we discovered that the 8 CLIA-confirmed positive samples were obtained from returned travellers who had visited China during the 4-week period immediately preceding blood donation.ConclusionIn conclusion, we found evidence to support the early circulation of SARS-CoV-2 among persons who visited China a few months prior to the pandemic declaration. These results can be used to better define the spread of SARS-CoV-2 infections before the COVID-19 pandemic declaration. The detection of SARS-CoV-2 antibodies in individuals before the pandemic was declared in China could rewrite the pre-pandemic timeline.

Generalized lymphadenopathy as an atypical initial clinical manifestation in rheumatoid arthritis and a possible hypothetical mechanism

Objective: To describe a 60-year-old male with diffuse generalized lymphadenopathy preceding a diagnosis of rheumatoid arthritis.Case presentation: The patient was admitted on suspicion of lymphoma. Chest positron emission/computed tomography showed enlarged lymph nodes bilaterally, mediastinum in the perihilar, retroperitoneum, and inguinal regions, with normal hematopoiesis of bone marrow. Lymph node biopsy revealed reactive follicular lymphadenopathy. Polyarthritis was present, and a rheumatoid factor test was positive eight months after the initial medical evaluation. A diagnosis of rheumatoid arthritis associated with generalized lymph node involvement was made. The patient was treated with leflunomide and corticosteroids and showed complete recovery without recurrence at 18 months of follow-up.Conclusions: Once histological findings of reactive lymph node hyperplasia are established as primarily related to rheumatic disease activity, clinicians should consider a possible diagnosis of rheumatoid arthritis.

Intraindividual Changes in Rheumatoid Factor and Anti-Cyclic Citrullinated Peptide Antibody Tests in Korean Patients Visiting Local Clinics and Hospitals.

Limited data are available on test utilization and intraindividual changes in rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (anti-CCP) in Korean patients that visit local clinics and hospitals. We retrospectively reviewed longitudinally measured RF and anti-CCP data in Korean patients to investigate the utilization and changes in test results through a laboratory information system. During the 10-year study period, 256,259 specimens were tested for RF. Among them, 32,567 (12.7%) specimens from 31,110 Korean adults had simultaneously measured anti-CCP results. Among them, 1110 (3.6%) subjects had follow-up test results. Among 351 patients with initial positive RF results, 290 (82.6%) had no qualitative change in RF from positive to negative values during follow-up. About 3.8% (29/759) of patients with initial negative results experienced qualitative changes in RF that were positive on follow-up. Among 182 patients with an anti-CCP-positive result at initial measurement, 174 (95.6%) had no qualitative change in anti-CCP from positive to negative or equivocal results during follow-up. About 0.5% (5/928) of patients with initial negative values experienced qualitative changes in anti-CCP to positive values on follow-up. The agreement of qualitative results between RF and anti-CCP was 80.8% (95% confidence interval 78.4–83.1%) at initial measurement and 80.6% (95% confidence interval 79.0–82.1%) overall. The results of this study can help inform utilization of RF and anti-CCP testing for Korean patients visiting local clinics and hospitals.

Serum protein electrophoresis and rheumatoid factor analysis as a screening strategy for cryoglobulinaemia

Introduction: Serum cryoglobulin detection is central to the diagnosis of cryoglobulinaemia, but laboratory testing has long turnaround times. Serum protein electrophoresis (EPG) and rheumatoid factor (RF) testing may be an effective initial screening strategy for the presence of cryoglobulinaemia.