The Homogeneous Multiplexed System-a New Method for Autoantibody Profile in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a multi-systemic autoimmune disease leading to immunological aberrations and excessive multiple autoantibody production. The aim of this study was to investigate the prevalence of multiple autoantibodies in SLE patients utilizing the multiplex system method

Familial Mediterranean Fever and Hyperimmunoglobulinemia D syndrome: two diseases with distinct clinical, serologic, and genetic features

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Mesenteric rheumatoid nodules masquerading as an intra-abdominal malignancy: a case report and review of the literature

<p>Abstract</p> <p>Background</p> <p>Rheumatoid nodules are the most common extra-articular findings in patients with rheumatoid arthritis. They occur most commonly at pressure points such as the extensor surfaces of the forearms, fingers, and occiput, but have also been reported to occur in unusual locations including the central nervous system, pericardium, pleura, and sclera. We present the unusual case of rheumatoid nodules in the small bowel mesentery masquerading as an intra-abdominal malignancy.</p> <p>Case presentation</p> <p>A 65-year-old-male with a known history of longstanding erosive, nodular, seropositive rheumatoid arthritis was incidentally found to have a mesenteric mass on computed tomography (CT) exam of the abdomen. This mass had not been present on prior imaging studies and was worrisome for a malignancy. Attempts at noninvasive biopsy were nondiagnostic but consistent with a "spindle" cell neoplasm. Laparotomy revealed extensive thickening and fibrosis of the small bowel mesentery along with large, firm nodules throughout the mesentery. A limited bowel resection including a large, partially obstructing, nodule was performed. Pathology was consistent with an unusual presentation of rheumatoid nodules in the mesentery of the small bowel.</p> <p>Conclusion</p> <p>Rheumatoid nodules should be considered in the differential diagnosis of a patient who presents with an intra-abdominal mass and a history of rheumatoid arthritis. Currently, no tests or imaging modality can discriminate with sufficient accuracy to rule out a malignancy in this difficult diagnostic delimma. Hopefully, this case will serve as impetus for further study and biomarker discovery to allow for improved diagnostic power.</p

Methotrexate enhances the anti-inflammatory effect of CF101 via up-regulation of the A(3 )adenosine receptor expression

Methotrexate (MTX) exerts an anti-inflammatory effect via its metabolite adenosine, which activates adenosine receptors. The A(3 )adenosine receptor (A(3)AR) was found to be highly expressed in inflammatory tissues and peripheral blood mononuclear cells (PBMCs) of rats with adjuvant-induced arthritis (AIA). CF101 (IB-MECA), an A(3)AR agonist, was previously found to inhibit the clinical and pathological manifestations of AIA. The aim of the present study was to examine the effect of MTX on A(3)AR expression level and the efficacy of combined treatment with CF101 and MTX in AIA rats. AIA rats were treated with MTX, CF101, or both agents combined. A(3)AR mRNA, protein expression and exhibition were tested in paw and PBMC extracts from AIA rats utilizing immunohistochemistry staining, RT-PCR and Western blot analysis. A(3)AR level was tested in PBMC extracts from patients chronically treated with MTX and healthy individuals. The effect of CF101, MTX and combined treatment on A(3)AR expression level was also tested in PHA-stimulated PBMCs from healthy individuals and from MTX-treated patients with rheumatoid arthritis (RA). Combined treatment with CF101 and MTX resulted in an additive anti-inflammatory effect in AIA rats. MTX induced A(2A)AR and A(3)AR over-expression in paw cells from treated animals. Moreover, increased A(3)AR expression level was detected in PBMCs from MTX-treated RA patients compared with cells from healthy individuals. MTX also increased the protein expression level of PHA-stimulated PBMCs from healthy individuals. The increase in A(3)AR level was counteracted in vitro by adenosine deaminase and mimicked in vivo by dipyridamole, demonstrating that receptor over-expression was mediated by adenosine. In conclusion, the data presented here indicate that MTX induces increased A(3)AR expression and exhibition, thereby potentiating the inhibitory effect of CF101 and supporting combined use of these drugs to treat RA

Methotrexate enhances the anti-inflammatory effect of CF101 via up-regulation of the A(3 )adenosine receptor expression

Methotrexate (MTX) exerts an anti-inflammatory effect via its metabolite adenosine, which activates adenosine receptors. The A(3 )adenosine receptor (A(3)AR) was found to be highly expressed in inflammatory tissues and peripheral blood mononuclear cells (PBMCs) of rats with adjuvant-induced arthritis (AIA). CF101 (IB-MECA), an A(3)AR agonist, was previously found to inhibit the clinical and pathological manifestations of AIA. The aim of the present study was to examine the effect of MTX on A(3)AR expression level and the efficacy of combined treatment with CF101 and MTX in AIA rats. AIA rats were treated with MTX, CF101, or both agents combined. A(3)AR mRNA, protein expression and exhibition were tested in paw and PBMC extracts from AIA rats utilizing immunohistochemistry staining, RT-PCR and Western blot analysis. A(3)AR level was tested in PBMC extracts from patients chronically treated with MTX and healthy individuals. The effect of CF101, MTX and combined treatment on A(3)AR expression level was also tested in PHA-stimulated PBMCs from healthy individuals and from MTX-treated patients with rheumatoid arthritis (RA). Combined treatment with CF101 and MTX resulted in an additive anti-inflammatory effect in AIA rats. MTX induced A(2A)AR and A(3)AR over-expression in paw cells from treated animals. Moreover, increased A(3)AR expression level was detected in PBMCs from MTX-treated RA patients compared with cells from healthy individuals. MTX also increased the protein expression level of PHA-stimulated PBMCs from healthy individuals. The increase in A(3)AR level was counteracted in vitro by adenosine deaminase and mimicked in vivo by dipyridamole, demonstrating that receptor over-expression was mediated by adenosine. In conclusion, the data presented here indicate that MTX induces increased A(3)AR expression and exhibition, thereby potentiating the inhibitory effect of CF101 and supporting combined use of these drugs to treat RA

Association between low-dose pulsed intravenous cyclophosphamide therapy and amenorrhea in patients with systemic lupus erythematosus: A case-control study

<p>Abstract</p> <p>Background</p> <p>The risk for amenorrhea following treatment of systemic lupus erythematosus (SLE) patients with low-dose intravenous cyclophosphamide (IVCY) has not been fully explored. Our objective was to ascertain the incidence of amenorrhea following treatment with low-dose IVCY and the association between amenorrhea and the clinical parameters of SLE.</p> <p>Methods</p> <p>A case-control retrospective study of premenopausal women ≤ 45 years old who had been treated for SLE with low-dose IVCY (500 mg/body/pulse) plus high-dose glucocorticoids (0.8-1.0 mg/kg/day of prednisolone; IVCY group) or glucocorticoids alone (0.8-1.0 mg/kg/day of prednisolone; steroid group) in our hospital from 2000 through 2009 was conducted using a questionnaire survey and medical record review.</p> <p>Results</p> <p>Twenty-nine subjects in the IVCY group and 33 subjects in the steroid group returned the questionnaire. A multivariate analysis revealed that age at initiation of treatment ≥ 40 years old was significantly associated with amenorrhea [<it>p </it>= 0.009; odds ratio (OR) 10.2; 95% confidence interval (CI) 1.8-58.7]. IVCY treatment may display a trend for association with amenorrhea (<it>p </it>= 0.07; OR 2.9; 95% CI 0.9-9.4). Sustained amenorrhea developed in 4 subjects in the IVCY group and 1 subject in the steroid group; all of these patients were ≥ 40 years old. Menses resumed in all subjects < 40 years old, irrespective of treatment.</p> <p>Conclusions</p> <p>Although low-dose IVCY may increase the risk for amenorrhea, our data suggest that patients < 40 years old have a minimum risk for sustained amenorrhea with low-dose IVCY treatment. A higher risk for sustained amenorrhea following treatment with IVCY is a consideration for patients ≥ 40 years old.</p

PEG Minocycline-Liposomes Ameliorate CNS Autoimmune Disease

Minocycline is an oral tetracycline derivative with good bioavailability in the central nervous system (CNS). Minocycline, a potent inhibitor of matrix metalloproteinase (MMP)-9, attenuates disease activity in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Potential adverse effects associated with long-term daily minocycline therapy in human patients are concerning. Here, we investigated whether less frequent treatment with long-circulating polyethylene glycol (PEG) minocycline liposomes are effective in treating EAE.Performing in vitro time kinetic studies of PEG minocycline-liposomes in human peripheral blood mononuclear cells (PBMCs), we determined that PEG minocycline-liposome preparations stabilized with CaCl(2) are effective in diminishing MMP-9 activity. Intravenous injections of PEG minocycline-liposomes every five days were as effective in ameliorating clinical EAE as daily intraperitoneal injections of minocycline. Treatment of animals with PEG minocycline-liposomes significantly reduced the number of CNS-infiltrating leukocytes, and the overall expression of MMP-9 in the CNS. There was also a significant suppression of MMP-9 expression and proteolytic activity in splenocytes of treated animals, but not in CNS-infiltrating leukocytes. Thus, leukocytes gaining access to the brain and spinal cord require the same absolute amount of MMP-9 in all treatment groups, but minocycline decreases the absolute cell number.Our data indicate that less frequent injections of PEG minocycline-liposomes are an effective alternative pharmacotherapy to daily minocycline injections for the treatment of CNS autoimmune diseases. Also, inhibition of MMP-9 remains a promising treatment target in EAE and patients with MS

Use of a gonadotropin-releasing hormone analog for protection against premature ovarian failure during cyclophosphamide therapy in women with severe lupus

Objective Cyclophosphamide (CYC) therapy for systemic lupus erythematosus (SLE), a disease predominantly affecting women of childbearing age, causes an unacceptably high incidence of irreversible premature ovarian failure (POF). This study was performed to evaluate the effectiveness of depot leuprolide acetate, a synthetic gonadotropin-releasing hormone analog (GnRH-a), for protection against POF during CYC therapy. Methods Young women with severe SLE treated in a standardized protocol of monthly intravenous bolus CYC were offered treatment with GnRH-a (depot leuprolide acetate; a 3.75-mg monthly injection during the standard CYC regimen). Patients treated with GnRH-a were compared with controls individually matched by age (±5 years) and by cumulative CYC dose (±5 gm). Reproductive status was determined after a minimum followup of 3 years after CYC therapy. The primary outcome was time to POF. Paired summary statistical analyses, Kaplan-Meier survival estimates, and Cox regression analyses were performed to assess differences in outcome between groups. Results POF developed in 1 of 20 women treated with GnRH-a (5%) compared with 6 of 20 controls (30%) matched by age and cumulative CYC dose (matched odds ratio 0.09, P < 0.05). Kaplan-Meier estimates demonstrated improved cumulative ovarian protection over time in the GnRH-a–treated group ( P = 0.04). Conclusion Treatment with GnRH-a during CYC therapy was associated with a significant reduction of POF in young women with severe SLE.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48676/1/21263_ftp.pd

Immune-Mediated Disease Flares or New-Onset Disease in 27 Subjects Following mRNA/DNA SARS-CoV-2 Vaccination

Background: Infectious diseases and vaccines can occasionally cause new-onset or flare of immune-mediated diseases (IMDs). The adjuvanticity of the available SARS-CoV-2 vaccines is based on either TLR-7/8 or TLR-9 agonism, which is distinct from previous vaccines and is a common pathogenic mechanism in IMDs. Methods: We evaluated IMD flares or new disease onset within 28-days of SARS-CoV-2 vaccination at five large tertiary centres in countries with early vaccination adoption, three in Israel, one in UK, and one in USA. We assessed the pattern of disease expression in terms of autoimmune, autoinflammatory, or mixed disease phenotype and organ system affected. We also evaluated outcomes. Findings: 27 cases included 17 flares and 10 new onset IMDs. 23/27 received the BNT - 162b2 vaccine, 2/27 the mRNA-1273 and 2/27 the ChAdOx1 vaccines. The mean age was 54.4 ± 19.2 years and 55% of cases were female. Among the 27 cases, 21 (78%) had at least one underlying autoimmune/rheumatic disease prior the vaccination. Among those patients with a flare or activation, four episodes occurred after receiving the second-dose and in one patient they occurred both after the first and the second-dose. In those patients with a new onset disease, two occurred after the second-dose and in one patient occurred both after the first (new onset) and second-dose (flare). For either dose, IMDs occurred on average 4 days later. Of the cases, 20/27 (75%) were mild to moderate in severity. Over 80% of cases had excellent resolution of inflammatory features, mostly with the use of corticosteroid therapy. Other immune-mediated conditions included idiopathic pericarditis (n = 2), neurosarcoidosis with small fiber neuropathy (n = 1), demyelination (n = 1), and myasthenia gravis (n = 2). In 22 cases (81.5%), the insurgence of Adverse event following immunization (AEFI)/IMD could not be explained based on the drug received by the patient. In 23 cases (85.2%), AEFI development could not be explained based on the underlying disease/co-morbidities. Only in one case (3.7%), the timing window of the insurgence of the side effect was considered not compatible with the time from vaccine to flare. Interpretation: Despite the high population exposure in the regions served by these centers, IMDs flares or onset temporally-associated with SARS-CoV-2 vaccination appear rare. Most are moderate in severity and responsive to therapy although some severe flares occurred. Funding: none