Tumor-like Lesions in Patients with Granulomatosis with Polyangiitis: A Case Series.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is a rare small vessel vasculitis. It usually involves the respiratory tract and kidney. Rarely, tumor-resembling inflammatory changes ensue. OBJECTIVES: To report three unique cases of GPA presenting with tumor-like lesions in various organs. METHODS: We presented three cases of GPA. Case 1 presented with typical upper respiratory symptoms of GPA and a mediastinal mass. Case 2 presented with low back pain, a large retroperitoneal mass, and nodular skin lesions. Case 3 presented with epigastric pain and a paravertebral inflammatory mass. RESULTS: The patients were treated successfully with rituximab. CONCLUSIONS: Clinicians should be aware of this presentation of granulomatosis with polyangiitis, which is known as Tumefaction Wegener's granulomatosis.

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.

Acute onset of psoriatic spondyloarthritis as a new manifestation of post-streptococcal reactive arthritis: a case series.

Streptococcus is well associated with a myriad of inflammatory diseases. Among others, this bacterium is linked to the triggering of psoriasis and to post-streptococcal reactive arthritis (PSRA), an arthritis which is typically confined to peripheral joints. Three patients who developed acute psoriatic spondyloarthritis (SpA) following a recent streptococcal infection are described in this article. We searched the existing literature for cases of axial involvement in PSRA and reviewed the association between streptococcal infection and psoriasis or psoriatic arthritis )PsA). In all patients, psoriatic SpA occurred within 7-10 days of a confirmed streptococcal infection. The main presenting syndrome was inflammatory back pain with evidence of acute axial spondyloarthritis on magnetic resonance imaging. One patient had guttate psoriasis, the second patient developed pustular psoriasis, and the third patient had exacerbation of pustular palmoplantar psoriasis. Two patients required treatment with tumor necrosis factor alpha (TNF-α) blockers. Axial involvement in PSRA is very rare. A potential association of streptococcal infection and development of PsA has been explored in several articles. However, to the best of our knowledge, acute psoriatic SpA as a manifestation of PSRA has yet to be described. Acute psoriatic SpA should be considered in the differential diagnosis of new-onset inflammatory back pain followed by psoriasis in young adults who had a recent throat infection. KEY POINTS: • Our case series describes three cases of acute psoriatic spondyloarthritis that occurred within 7--10 days of a confirmed streptococcal infection and progressed to full blown chronic disease. • Acute psoriatic spondyloarthritis as a manifestation of post streptococcal reactive arthritis should be considered in the differential diagnosis of new onset inflammatory back pain followed by psoriasis in young adults who had a recent throat infection.

Efficacy and survival of golimumab with and without methotrexate in patients with psoriatic arthritis: A retrospective study from daily clinical practice.

Golimumab is a recombinant human monoclonal antibody targeted against tumour necrosis factor-alpha (TNF-α). Golimumab is effective in the management of patients with active psoriatic arthritis (PsA). The aim of this study is to evaluate the clinical efficacy and survival of golimumab monotherapy versus co-administration with methotrexate (MTX) in patients with PsA in the clinical practice. This retrospective observational trial included patients with PsA. Efficacy was assessed by disease activity scores - DAS28, BASDAI, physician global assessment of disease (PGA) and CRP. Golimumab survival rate was estimated using the Kaplan-Meier analysis and univariate and multivariate Cox regression models. Forty-one patients with PsA were recruited; 26 patients were treated with golimumab, whereas 15 patients received combination therapy with MTX. The treatment resulted in significantly improved clinical measures of disease activity in comparison with baseline, including DAS28 CRP (4.1 vs 2.6, p ≤ 0.0001) and BASDAI (5.6 vs 3.8, p ≤ 0.001). Overall, 29 (71%) patients continued golimumab treatment (18 patients on monotherapy and 11 on combination therapy). The difference in the duration of golimumab survival between the combination therapy and monotherapy groups was not statistically significant (12.5 vs 12 months, p = 0.2). Similar efficacy profiles and survival rates were documented in patients with PsA regardless of the co-administration of methotrexate.

Extrapyramidal signs in neurosarcoidosis versus multiple sclerosis: Is TNF alpha the link?

Specific inflammatory pathways and specifically Tumor Necrosis Factor alpha (TNF-α) have been associated with the neurodegeneration in Parkinson's disease (PD). TNFα is also known to play an important role in the pathogenesis of sarcoidosis and TNF blockers can ameliorate the disease. In contrast, multiple sclerosis (MS) is clearly exacerbated by anti- TNF-α medications. We have therefore hypothesized that Parkinson-like disease would be more common in neurosarcoidosis (NS) compared to MS. The aim of this case-control study was therefore to assess the frequency of extrapyramidal signs in patients with NS compared to MS patients. In order to do so the medical records of NS patients and of age and gender matched MS patients were reviewed and data regarding the clinical features, ancillary tests performed, treatment, and outcome were documented. Patients were then examined in a uniform manner for the presence of extrapyramidal signs. We found that in the NS group 8 patients had minor signs, one had mild functional disability and 3 subjects had significant extrapyramidal signs compatible with the diagnosis of Parkinson's disease. All extrapyramidal signs found in 5 of the MS group were minor. The proportional severity of extrapyramidal signs was significantly higher (p=0.045, chi square test) in the NS group compared to the MS group. We conclude that the specificity of extrapyramidal to NS raises the intriguing question of whether specific inflammatory pathways involving TNF-α play a role in the pathogenesis of PD and therefore may be a therapeutic target.

The prevalence and clinical effect of immunogenicity of TNF-α blockers in patients with axial spondyloarthritis.

OBJECTIVES: To evaluate the prevalence of immunogenicity of TNF-α blockers in axial spondyloarthritis (SpA) patients and to assess the effect of immunogenicity on drug levels and clinical response. METHPDS: Patients with axial SpA treated with either infliximab (INF), adalimumab (ADA) or etanercept (ETN) were recruited to our observational cross-sectional study. Demographic and clinical data were collected and disease activity scores were assessed. Drug trough levels and anti-drug antibodies were measured in serum samples and collected before the next administration. RESULTS: Thirty-nine patients with axial SpA with a mean age of 46.3±12.7 (10 women) were recruited to the study (14 receiving INF, 16 ADA and 9 ETN). Patients' mean therapy duration was 50.6 months (±46.4) and 6 (15%) of them were using MTX concomitantly with the TNF-α blockers. Anti-drug antibodies were found in 6 (15%) patients (4 with INF and 2 with ADA), all of which had undetectable drug level. No anti-drug antibodies were detected in patients treated with ETN. Immunogenicity was associated with higher BASDAI (Bath Ankylosing Spondylitis Disease Index), ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score) and ASDAS-ESR. CONCLUSIONS: Axial SpA patients failure to respond to TNF-α blockers may be at least partially related to immunogenicity. Measurement of anti-drug antibodies and drug levels in these patients may assist in determining further treatment strategies.

Rhupus; unusual presentations.

BACKGROUND: The coexistence of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) named Rhupus is an unusual clinical condition. Previous reports mentioned that Rhupus patients have prominent RA-associated clinical manifestations and only mild organic damage related to SLE. Progressive or life-threatening manifestations are rare in Rhupus patients. METHODS: Three patients with Rhupus are described in this article. Two of them presented antiphospholipid syndrome (APS) in addition to Rhupus. Also, we searched for similar cases in published literature. RESULTS: We present three patients with Rhupus syndrome. One of the patients has only Rhupus, the second patient has Rhupus and APS, and the third patient has Rhupus accompanied by severe Raynaud's syndrome with digital ulcers, APS, pulmonary hypertension and two malignancies. Several studies have shown that Rhupus patients have an increased prevalence of positive antiphospholipid antibodies that resembles SLE. However, the presence of these antibodies is not associated with APS. There is only one case of Rhupus with secondary APS in which the patient presented headache and papilloedema due to cerebral venous thrombosis. Secondary Raynaud's syndrome is rare in Rhupus patients, and to the best of our knowledge, only three cases of this are mentioned in literature. Secondary pulmonary hypertension and malignancies were never reported before in Rhupus patients. CONCLUSIONS: Rheumatologists should be aware of the possibility that Rhupus may be accompanied by progressive or life-threatening conditions such as APS, severe Raynaud's syndrome with digital ulcers, pulmonary hypertension, or malignancies.

Plaque morphea with neurological involvement­an extraordinary uncommon presentation.

Localized scleroderma is traditionally considered to be limited to the skin, subcutaneous tissue, underlying bone, and in the craniofacial subtype, also nervous system involvement. However, recent studies have also described other systemic manifestations in these patients. Despite many reports of neurological involvement in patients with the craniofacial linear localized scleroderma, it is extremely rare in patients with the other subtypes of localized scleroderma. Here, we report an extraordinary case of localized scleroderma en plaque (classic morphea), located to the upper trunk and neck, associated with neurological manifestations presented as seizures. Magnetic resonance imaging of the brain showed focal lesions on the contralateral side to the skin involvement. This case is extremely relevant not only due to its rarity, but also because it supports the idea that the pathogenesis of the localized scleroderma is related to a systemic autoimmune process.

Olfactory impairment in patients with the fibromyalgia syndrome and systemic sclerosis.

Patients with autoimmune diseases often present with olfactory impairment. The aim of the study was to assess the olfactory functions of female patients with fibromyalgia (FM) compared with patients with systemic sclerosis (SSc) and with healthy female controls. Olfactory functions were assessed in 24 patients with FM, 20 patients with SSc and 21 age-matched healthy controls. The sense of smell was evaluated using the Sniffin' Sticks test including the three stages of smell: threshold, discrimination, and identification (TDI) of the different odors. The severity of fibromyalgia was assessed using the fibromyalgia impact questionnaire (FIQ). The short form 36 (SF-36) questionnaire was also completed in order to seek a relationship between the patients perception of quality of life and the different aspects of the smell sense. Depression was evaluated in both FM and SSc patients utilizing the Beck depression inventory-II (BDI-II) questionnaire. Patients with FM had significantly lower TDI smell scores compared with both SSc patients and healthy controls (p < 0.005, One-Way ANOVA). Hyposmia (defined as TDI scores below 30) were observed in 14 of 24 (42 %) patients with FM compared to 3 of 20 (15 %) patients with SSc and 1 of the healthy controls (4.3 %) (p < 0.02). FM patients had significantly lower thresholds of smell compared to both healthy controls and patients with SSc (p < 0.001), whereas for patients with SSc only the ability to discriminate between odors was impaired (p < 0.006). We could not detect any statistical correlation between smell abilities and clinical manifestation of SSc or the FIQ and SF-36 scores among FM patients. However the correlation between depression, defined by the BDI-II score, and the sense of smell differed between patients with FM and patients with SSc. As only among SSc patients a lower sense of smell correlated with a higher BDI-II score (p = 0.02). Our findings suggest that there is a decrease in the sense of smell both in FM and SSc patients compared with healthy controls. However these impairments differ between patients group and might represent different mechanisms that affect the sense of smell.

Epstein-Barr virus antibodies mark systemic lupus erythematosus and scleroderma patients negative for anti-DNA.

Systemic lupus erythematosus (SLE) is an autoimmune disease that can attack many different body organs; the triggering event is unknown. SLE has been associated with more than 100 different autoantibody reactivities - anti-dsDNA is prominent. Nevertheless, autoantibodies to dsDNA occur in only two-thirds of SLE patients. We previously reported the use of an antigen microarray to characterize SLE serology. We now report the results of an expanded study of serology in SLE patients and scleroderma (SSc) patients compared with healthy controls. The analysis validated and extended previous findings: two-thirds of SLE patients reacted to a large spectrum of self-molecules that overlapped with their reactivity to dsDNA; moreover, some SLE patients manifested a deficiency of natural IgM autoantibodies. Most significant was the finding that many SLE patients who were negative for autoantibodies to dsDNA manifested abnormal antibody responses to Epstein-Barr virus (EBV): these subjects made IgG antibodies to EBV antigens to which healthy subjects did not respond or they failed to make antibodies to EBV antigens to which healthy subjects did respond. This observation suggests that SLE may be associated with a defective immune response to EBV. The SSc patients shared many of these serological abnormalities with SLE patients, but differed from them in increased IgG autoantibodies to topoisomerase and centromere B; 84% of SLE patients and 58% of SSc patients could be detected by their abnormal antibodies to EBV. Hence an aberrant immune response to a ubiquitous viral infection such as EBV might set the stage for an autoimmune disease.

[Guidelines for the diagnosis and treatment of the fibromyalgia syndrome].

Over the past years, considerable progress has been made in understanding the pathogenesis of the fibromyatgia syndrome and the evidence based approach to the diagnosis and management has been significantty extended. The purpose of the current project is to develop practicat and evidence based guidetine recommendations for the Israeli health care system. A panet of physicians with clinical and research experience in the fibromyalgia field was convened under the auspices of the Israeli Rheumatology Association. A systematic review was performed on the current literature regarding the diagnosis and treatment of fibromyalgia. Using an interactive discussion procedure, recommendations were reached and expert opinion was introduced where evidence was considered incomplete. The panel recommendations underline the importance of concomitant and integrated medical therapy, such as serotonin and noradrenaline reuptake inhibitor (SNRI) anti-depressants or gamma-aminobutyric acid (GABA) related anti-epileptics, with regular aerobic physical exercise.

Incomplete response to colchicine in M694V homozygote FMF patients.

BACKGROUND: Previous studies have shown that with prophylactic colchicine 65% of the patients suffering from Familial Mediterranean fever (FMF) will show a complete response, 30% a partial response and about 5% will show minimum or no response. These studies were performed before the isolation of the disease gene. Genotyping enables us to study the response rates according to specific mutations. We have witnessed a large number of M694V homozygotes who do not respond well to colchicine despite being treated with maximal sustained doses. AIM: To assess the response rates to colchicine in M694V homozygote FMF patients in comparison to other prevalent genotypes. METHODS: We conducted a telephonic survey which included 112 FMF patients: 40 M694V homozygotes, and 2 comparison groups of 41 M694V/V726A compound heterozygotes and 31 V726A homozygotes. The questionnaire included demographic, social and clinical features, colchicine dose, response rates and reported side effects. RESULTS: M694 homozygotes showed a more severe disease, and were treated with higher doses of colchicine (average dose 1.98±0.56 compared to 1.47±0.58, p=0.0001 and 1.13±0.41, p<0.001 in the M694V/V726A compound heterozygotes and the V726A homozygotes, respectively); Colchicine related side effects were noted in 40% of the M694V homozygotes. The average rate of attacks in treated M694V homozygotes (0.70±1.06) was higher compared to the two other groups (0.14±0.26, p=0.002 and 0.08±0.20, p=0.0009, respectively) and only 25% of them reported no attacks in the last year. None of the patients who took part in this study had amyloidosis. Side effects limiting the dose of colchicine were noted in 40% of the M694V homozygotes. CONCLUSIONS: Despite receiving higher doses of colchicine the prevalence of complete responders among M694V homozygotes is much lower than previously appreciated. The results highlight the need for additional treatment modalities for these patients.

Infectious serologies and autoantibodies in hepatitis C and autoimmune disease-associated mixed cryoglobulinemia.

Mixed cryoglobulinemia (MC) syndrome is an immune complex-mediated vasculitis characterized by the clinical triad of purpura, weakness, and arthralgias, the morbidity of which is mainly related to kidney and peripheral nervous system dysfunction as well as to the development of a secondary lymphoma (Ferri et al. Autoimmun Rev 7:114-120, 2007, Lidar et al. Ann N Y Acad Sci 1173:649-657, 2009, Trejo et al. Semin Arthritis Rheum 33:19-28, 2003). MC is associated with infectious and systemic disorders, principally autoimmune and lymphoproliferative diseases. Since the 1990s, a striking association (>90%) between MC and hepatitis C virus (HCV) infection has been established (Ferri and Bombardieri 2004; Pascual et al. J Infect Dis 162:569-570, 1990). However, information regarding the etiopathogenesis of HCV-negative MC is scant (Mascia et al. Dig Liver Dis 39:61-64, 2007). We hereby present our findings, as well as previously published data, regarding the presence of antibodies against infectious agents and autoantibodies in patients with MC in an attempt to establish novel associations which may shed light on the etiopathogenesis of this disease.

Hydroxychloroquine: from malaria to autoimmunity.

Quinine was first recognized as a potent antimalarial agent hundreds of years ago. Since then, the beneficial effects of quinine and its more advanced synthetic forms, chloroquine and hydroxychloroquine, have been increasingly recognized in a myriad of other diseases in addition to malaria. In recent years, antimalarials were shown to have various immunomodulatory effects, and currently have an established role in the management of rheumatic diseases, such as systemic lupus erythematosus and rheumatoid arthritis, skin diseases, and in the treatment of chronic Q fever. Lately, additional metabolic, cardiovascular, antithrombotic, and antineoplastic effects of antimalarials were shown. In this review, we discuss the known various immunomodulatory mechanisms of antimalarials and the current evidence for their beneficial effects in various diseases and in potential novel applications.

Normal autonomic nervous system responses in uncomplicated familial Mediterranean fever: a comparative case-control study.

There is a paucity of knowledge regarding the autonomic nervous system function in patients with familial Mediterranean fever (FMF). Therefore, our aim was to evaluate autonomic responses in patients with FMF using complementary tests. The study groups included 33 patients with uncomplicated FMF and 39 control subjects. Autonomic function was evaluated by measuring responses to metronomic breathing, the Valsalva maneuver, and the Ewing maneuver. Autonomic parameters were computed from electrocardiograms with designated computer software. There were no statistically significant differences in any of the measured parameters of autonomic function between the patient and control group. The measured autonomic parameters of both groups were similar to those previously reported in healthy individuals. In conclusion, patients with FMF who did not develop amyloidosis due to continuous colchicine treatment appeared to have normal autonomic function, as reflected by the normal response to physiological autonomic stimuli.

Vitamin D and autoimmune thyroid diseases.

The role of vitamin D as an immune modulator has been emphasized in recent years, and low levels of the hormone were observed in several autoimmune diseases including multiple sclerosis and systemic lupus erythematosus. Vitamin D mediates its effect though binding to vitamin D receptor (VDR), and activation of VDR-responsive genes. While VDR gene polymorphism was found to associate with autoimmune thyroid diseases (AITDs), few studies examined levels of vitamin D in these patients and those that did yielded conflicting results. We therefore undertook to evaluate the levels of vitamin D in patients with AITDs compared to patients with non-AITDs and healthy controls. Serum vitamin D (25-OH) levels were measured in 50 patients with AITDs, 42 patients with non-AITDs and 98 healthy subjects, utilizing the LIAISON chemiluminescence immunoassay (DiaSorin, Saluggia, Italy). Vitamin D deficiency was designated at levels lower than 10 ng/ml. Antithyroid antibodies, thyroid functions and demographic parameters were evaluated in all patients. The prevalence of vitamin D deficiency was significantly higher in patients with AITDs compared with healthy individuals (72% versus 30.6%; P<0.001), as well as in patients with Hashimoto's thyroiditis compared to patients with non-AITDs (79% versus 52%; P<0.05). Vitamin D deficiency also correlated to the presence of antithyroid antibodies (P=0.01) and abnormal thyroid function tests (P=0.059). Significantly low levels of vitamin D were documented in patients with AITDs that were related to the presence of anti thyroid antibodies and abnormal thyroid function tests, suggesting the involvement of vitamin D in the pathogenesis of AITDs and the advisability of supplementation.

Heart rate variability in familial Mediterranean fever.

Familial Mediterranean fever (FMF) is a hereditary disease, characterized by recurrent episodes of fever and polyserositis. Heart rate variability (HRV) is a powerful, simple and reliable technique to evaluate autonomic nervous system function. Previous studies of physiologic parameters during tilt-test have suggested that patients with FMF have abnormal cardiovascular reactivity and occult dysautonomia. Prompted by these findings, the present study sought to evaluate HRV in patients with FMF, at rest and in the standing position. The study sample included 34 patients with FMF and 34 sex- and age-matched control subjects. All underwent electrocardiography according to strict criteria. HRV parameters were computed with custom-made software. There was no significant difference in HRV parameters, in either the supine or standing position, between the FMF and control groups. In both groups, the upright position was associated with a significant decrease, when compared with the supine position, in maximal RR interval, minimal RR, average RR, root square of successive differences in RR interval, number of intervals differing by >50 ms from preceding interval (NN50), NN50 divided by total number of intervals (pNN50) and high-frequency components as well as a significant increase in average heart rate, very low frequency or low-frequency components, low-frequency/high-frequency components ratio and total power. In conclusion, patients with FMF who are continuously treated with low-dose colchicine have not developed amyloidosis and have normal HRV parameters in the supine and upright position. Further investigation of occult dysautonomia in FMF is needed.

Role of the R92Q TNFRSF1A mutation in patients with familial Mediterranean fever.

OBJECTIVE: To define the frequency of the R92Q tumor necrosis factor receptor-associated periodic syndrome (TRAPS) mutation in patients with familial Mediterranean fever (FMF) and to study the role of this mutation in FMF. METHODS: Ninety-two FMF patients and 250 controls were genotyped for the R92Q mutation. The frequency of R92Q was assessed among 5 groups of FMF patients. RESULTS: R92Q was found in 6% of the controls, with an especially high carrier rate among Moroccan Jews (8%). R92Q was found in 3 (3.2%) of the 92 FMF patients, 1 homozygous for the MEFV M694V mutation and 2 heterozygous for M694V. All 3 patients showed partial response to colchicine. R92Q was not found in patients unresponsive to colchicine, nor was it found in patients with amyloidosis or in patients with FMF-like disease without MEFV mutations. CONCLUSION: The frequency of the R92Q mutation in FMF patients is comparable with that of controls. Despite the fact that TRAPS and FMF share common biochemical pathways, we found no evidence for an interaction between these two genes.

QT dispersion in uncomplicated familial Mediterranean fever.

The aim of the study was to further evaluate repolarization dispersion in familial Mediterranean fever (FMF). Findings on 12-lead electrocardiography were compared with 32 patients with uncomplicated FMF and age- and sex-matched control subjects. All procedures followed stringent standards. Repolarization and dispersion parameters were computed with designated computer software, and results of the five beats were subsequently averaged. There were no statistically significant differences between the groups in average QT and average corrected QT interval length, average QT interval dispersion, average QT corrected dispersion, or QT dispersion ratio. During 6 months of follow-up, no cases of sudden death or arrhythmia were documented in either group. Patients with FMF who are continuously treated with low-dose colchicine and have not developed amyloidosis seem to have QT dispersion parameters similar to those of healthy subjects and therefore apparently have no increased risk of adverse cardiac events associated with abnormal repolarization.

An antibody profile of systemic lupus erythematosus detected by antigen microarray.

SUMMARY: Patients with systemic lupus erythematosus (SLE) produce antibodies to many different self-antigens. Here, we investigated antibodies in SLE sera using an antigen microarray containing many hundreds of antigens, mostly self-antigens. The aim was to detect sets of antibody reactivities characteristic of SLE patients in each of various clinical states--SLE patients with acute lupus nephritis, SLE patients in renal remission, and SLE patients who had never had renal involvement. The analysis produced two novel findings: (i) an SLE antibody profile persists independently of disease activity and despite long-term clinical remission, and (ii) this SLE antibody profile includes increases in four specific immunoglobulin G (IgG) reactivities to double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), Epstein-Barr virus (EBV) and hyaluronic acid; the profile also includes decreases in specific IgM reactivities to myeloperoxidase (MPO), CD99, collagen III, insulin-like growth factor binding protein 1 (IGFBP1) and cardiolipin. The reactivities together showed high sensitivity (> 93%) and high specificity for SLE (> 88%). A healthy control subject who had the SLE antibody profile was later found to develop clinical SLE. The present study did not detect antibody reactivities that differentiated among the various subgroups of SLE subjects with statistical significance. Thus, SLE is characterized by an enduring antibody profile irrespective of clinical state. The association of SLE with decreased IgM natural autoantibodies suggests that these autoantibodies might enhance resistance to SLE.