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2.
Hum Immunol ; 85(1): 110747, 2024 Jan.
Article En | MEDLINE | ID: mdl-38155072

INTRODUCTION: Silicone breast implants (SBI) result in immune dysregulation and are associated with autoimmune diseases. Recently, we reported dysregulated levels of IgG autoantibodies directed against G protein-coupled receptors (GPCRs) of the autonomic nervous system which were linked to the autoimmune dysautonomia in silicone breast implant illness (SBII). AIMS: We aimed to explore the possible association between allergy with dysregulated IgE autoantibodies directed against GPCRs of the autonomic nervous system in women with SBI. METHODS: Circulating levels of IgE autoantibodies against GPCRs of the autonomic nervous system (adrenergic, muscarinic, endothelin and angiotensin receptors) have been evaluated in women with SBIs who complained of allergic symptoms, and compared to subjects with SBI without allergic manifestations and to age-matched healthy women without SBI. RESULTS: We report a significant dysregulation in three circulating autoantibodies: IgE-beta1 adrenergic receptor (B1AR), IgE-alpha 1 adrenergic receptor (A1AR) and IgE-muscarinic acetylcholine receptor type 1 (M1R) autoantibodies in women with SBI who complained of allergic symptoms. CONCLUSIONS: Allergic reactions associated with SBI are not uncommon. Imbalance of circulating levels of IgE autoantibodies against GPCRs of the autonomic nervous system might play a role not only in allergic reactions, but also in other enigmatic aspects of SBII such as autoimmune dysautonomia.


Autonomic Nervous System Diseases , Breast Implants , Hypersensitivity , Humans , Female , Breast Implants/adverse effects , Autoantibodies , Receptors, G-Protein-Coupled , Silicones/adverse effects , Immunoglobulin E
4.
Rheumatol Ther ; 8(1): 631-637, 2021 Mar.
Article En | MEDLINE | ID: mdl-33527325

Chikungunya virus (CHIKV) infection is caused by an arbovirus prevalent in various parts of the world. The virus can induce autoantibodies and rheumatic diseases, such as rheumatoid arthritis and spondylarthritis. However, until now, no case of Sjögren syndrome (SS) was described associated with CHIKV. In this article, we describe a 49-year-old female with polyarthralgia and a temporary rash on her trunk and arms. Her physical examination showed polyarthritis of her ankles and wrists. Serologies for CHIKV were interpreted as positive with IgM 6.5 (normal range < 0.8) and negative for IgG. Antinuclear antibodies were positive at a titer of 1:640 as well as anti-Ro/SS-A. The diagnosis of subacute CHIKV infection was determined. The Schirmer test, Rose Bengal, and salivary scintigraphy were positive and the diagnosis of SS was confirmed. She was treated with hydroxychloroquine, methotrexate, and a single dose of betamethasone depot. This is the first report on CHIKV associated with SS. Sequence analysis of the CHIKV proteome versus SS autoantigens showed an extensive peptide sharing between the virus and numerous SS autoantigens, thus supporting the hypothesis that autoimmune cross-reactivity might causally link CHIKV to SS.

5.
Clin Rheumatol ; 38(5): 1257-1262, 2019 May.
Article En | MEDLINE | ID: mdl-30628015

Type I cryoglobulinemia is associated with B cell proliferative diseases, whereas essential mixed cryoglobulinemia is classically associated with infections, malignancy, and autoimmune diseases, but may be idiopathic. Prognosis in patients with grave manifestations and renal involvement is often poor. We report a case of a 40-year-old woman, 2 weeks post-partum for pre-eclampsia who was hospitalized with nephritic syndrome and acute renal failure. The patient harbored type I and type II cryoglobulinemia. Renal and cutaneous biopsies confirmed the diagnosis; however, an underlying etiology was not established. A bone marrow biopsy suggested monoclonal gammopathy of undetermined source (MGUS). Despite therapy with intravenous cyclophosphamide, rituximab, plasmapheresis, dialysis, and bortezomib, the patient succumbed after 8 months of hospitalization. We suggest that an overlap entity of types I and II cryoglobulinemia with severe multi-organ involvement not only is rare but also may be resistant to conventional therapy and fatal.


Cryoglobulinemia/complications , Cryoglobulinemia/therapy , Monoclonal Gammopathy of Undetermined Significance/complications , Monoclonal Gammopathy of Undetermined Significance/therapy , Adult , Cyclophosphamide , Dialysis , Fatal Outcome , Female , Humans , Immunoglobulin kappa-Chains/analysis , Kidney/pathology , Plasmapheresis , Rituximab , Skin/pathology
8.
Curr Opin Rheumatol ; 29(4): 389-393, 2017 07.
Article En | MEDLINE | ID: mdl-28376065

PURPOSE OF REVIEW: Chikungunya virus (CHIKV) is a mosquito-borne alphavirus. Fever, rash and severe arthralgia are the hallmarks of chikungunya fever (CHIKF), the disease caused by this virus. The acute course of the disease usually lasts few weeks to months. Chronic, relapsing or persistent arthralgia and arthritis have been described mimicking rheumatoid arthritis (RA), requiring immunosuppressive drugs.The purpose of this review is to characterize both the chronic clinical course of CHIKF-associated arthritis and the immunological pathogenic mechanisms involved. RECENT FINDINGS: The effect of postepidemic chronic persistent rheumatic course on the functional status of affected individuals, affecting large populations, has been studied. One-third of affected individuals had persistent pain months to years postepidemic and the identified risk factors for functional disability were identified.Inflammatory biomarkers associated with disease severity of RA such as interleukin 6 (IL6), and relevant chemokines have been found to correlate with the severity of postepidemic chronic disease. There are conflicting reports on antinuclear antibodies (ANAs) as well as rheumatoid factor and anti-citrullinated peptide antibody (ACPA) sero-positivity during infections.According to a recent study, eight out of 10 infected individuals developed chronic persistent rheumatic course and met classification criteria for seronegative RA.In a flow cytology analyses, these eight patients, similar to a group of RA patients, had a greater percentage of activated and effector CD4 and CD8 T cells than healthy controls. SUMMARY: Patients with CHKV infections may have a chronic persistent course of musculoskeletal disease, overlapping clinical and immunologic features with RA patients. In the appropriate setting and awareness, CHIKV infection should be considered when a patient is evaluated with a new symmetric polyarthritis.The question to be raised: Is it possible that in genetic prone individuals and in a particular environmental and infectious setting, such as CHIKF outbreak, an autoimmune disease will emerge?


Arthritis/immunology , Autoimmune Diseases/immunology , Chikungunya Fever/immunology , Antibodies, Antinuclear/immunology , Arthritis/epidemiology , Arthritis/virology , Arthritis, Rheumatoid/epidemiology , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/virology , Autoimmune Diseases/epidemiology , Autoimmune Diseases/virology , Autoimmunity/immunology , CD8-Positive T-Lymphocytes/immunology , Chikungunya Fever/epidemiology , Chikungunya virus/immunology , Humans , Interleukin-6/immunology , Peptides, Cyclic/immunology , Rheumatoid Factor/immunology
9.
Isr Med Assoc J ; 18(3-4): 162-3, 2016.
Article En | MEDLINE | ID: mdl-27228635

Chikungunya fever (CHIK-F) has been increasingly documented among Western travelers returning from areas with chikungunya virus transmission, which are also popular tourist sites. We present three Israeli travelers who developed fever, maculopapular rash and long-standing arthralgias while visiting northern Indian states not known to be involved in the chikungunya fever epidemic. We also present an epidemiological review of the chikungunya epidemic over the past decades. Rare systemic manifestations of this disorder, like catastrophic antiphospholipid syndrome (CAPS) and adult-onset Still's syndrome, are discussed. The present era of international travel poses a new diagnostic and epidemiologic challenge that demands increased awareness to the possibility of an exotic tropical infectious disease.


Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Chikungunya Fever , Culicidae , Endemic Diseases , Insect Vectors , Adult , Animals , Antiphospholipid Syndrome/etiology , Arthritis/etiology , Chikungunya Fever/diagnosis , Chikungunya Fever/drug therapy , Chikungunya Fever/epidemiology , Chikungunya Fever/physiopathology , Chikungunya Fever/transmission , Exanthema/etiology , Female , Humans , India/epidemiology , Israel/epidemiology , Male , Middle Aged , Serologic Tests/methods , Still's Disease, Adult-Onset/etiology , Travel
12.
J Travel Med ; 15(5): 382-4, 2008.
Article En | MEDLINE | ID: mdl-19006519

Chikungunya fever has been increasingly documented among Western travelers returning from areas with chikungunya virus transmission, which are also popular touristic sites. We describe the case of three Israeli travelers who developed fever, maculopapular rash, and long-standing arthralgias while visiting northern Indian states not known to be involved in the chikungunya fever epidemic.


Alphavirus Infections/diagnosis , Alphavirus Infections/therapy , Chikungunya virus/isolation & purification , Adult , Female , Fever/virology , Humans , India , Israel , Male , Middle Aged , Risk Factors , Tropical Climate
13.
Int J Dermatol ; 47(8): 790-5, 2008 Aug.
Article En | MEDLINE | ID: mdl-18717857

BACKGROUND: Atopic dermatitis is a common allergic condition in children, often associated with a positive skin reaction to house dust mite allergens. AIM: To determine the presence of house dust mites on the skin, clothes, and bedding of patients with atopic dermatitis. METHODS: Nineteen patients with atopic dermatitis were examined during a 2-year period. Samples from affected and healthy skin surfaces were obtained with adhesive tape, and dust samples from bedding and clothes were collected with a vacuum cleaner at the start of the study and 3-6 weeks later, and examined for the presence of house dust mites. The findings were compared with those of 21 healthy controls. RESULTS: The most common mite species on skin were Dermatophagoides pteronyssinus and Dermatophagoides farinae, which were found in nine patients and three controls. The patient group showed a significantly larger percentage of samples with mites than did the control group (34.9% and 7.9%, respectively) (P < 0.001), and a significantly larger percentage of individuals with at least one positive sample (84.2% and 14.2%, respectively) (P < 0.0001). No correlation was found between the number of mites on the skin and clothes/bedding of patients, or between patients and controls with regard to the number of mites on the clothes and bedding. CONCLUSIONS: Patients with atopic dermatitis showed a higher prevalence of mites on their skin than did healthy individuals, which could be involved in allergic sensitization and disease exacerbation.


Antigens, Dermatophagoides/immunology , Dermatitis, Atopic/epidemiology , Dermatitis, Atopic/immunology , Pyroglyphidae/immunology , Adolescent , Adult , Age Distribution , Animals , Bedding and Linens , Case-Control Studies , Chi-Square Distribution , Child , Child, Preschool , Clothing , Dermatitis, Atopic/etiology , Desensitization, Immunologic/methods , Female , Follow-Up Studies , Humans , Incidence , Infant , Male , Probability , Reference Values , Risk Factors , Sex Distribution , Skin Tests/methods
14.
J Rheumatol ; 35(1): 41-8, 2008 Jan.
Article En | MEDLINE | ID: mdl-18050382

OBJECTIVE: Adenosine exerts antiinflammatory effects via activation of the A3 adenosine receptor (A3AR), a Gi protein-associated cell-surface receptor, overexpressed in synovial tissue and peripheral blood mononuclear cells (PBMC) in patients with active rheumatoid arthritis (RA). CF101 is a highly specific orally bioavailable A3AR agonist. METHODS: This was a multicenter study, blinded to dose, designed to assess the clinical activity and safety of CF101 in active RA. Seventy-four patients were randomized to receive 0.1, 1.0, or 4.0 mg CF101 bid for 12 weeks. The primary efficacy endpoint was American College of Rheumatology 20% response (ACR20) at Week 12. A3AR expression levels were analyzed in PBMC from 18 patients. RESULTS: . Maximal responses were observed with 1.0 mg bid, lower at 0.1 and 4.0 mg bid. At 12 weeks, 55.6%, 33.3%, and 11.5% of the patients receiving 1.0 mg CF101 achieved ACR20%, 50%, and 70% responses, respectively. CF101 was generally well tolerated, with mild headache (4.1%), nausea (2.7%), and rash (2.7%) being the most common treatment-related adverse events. Statistically significant correlations between A3AR overexpression at baseline and ACR50 and ACR70 responses were observed. CONCLUSION: CF101 administered bid for 12 weeks resulted in improvement in signs and symptoms of RA that did not achieve statistical significance, and was safe and well tolerated. The expression level of A3AR was directly correlated with patient responses to CF101, suggesting its utilization as a biomarker for the pharmacodynamic and therapeutic effects of this novel agent. These findings require confirmation in a double-blind randomized placebo-controlled trial, currently under way.


Adenosine/analogs & derivatives , Arthritis, Rheumatoid/drug therapy , Receptor, Adenosine A3/drug effects , Adenosine/administration & dosage , Adenosine/adverse effects , Adenosine A3 Receptor Agonists , Adult , Aged , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Severity of Illness Index , Treatment Outcome
15.
Ann N Y Acad Sci ; 1108: 24-34, 2007 Jun.
Article En | MEDLINE | ID: mdl-17893967

We studied the large and small artery elasticity (AE) and systemic vascular resistance (SVR) of systemic lupus erythematosus (SLE) patients according to treatment profile. Forty-one SLE patients (90% female, mean age 48.7 +/- 2.4 years) were compared to 96 healthy controls. The large and small AE and the SVR were derived from radial artery waveforms (model CR-2000, HDI Inc.). Patients were categorized into groups according to treatment: steroid (12), hydroxychloroquine (HCQ) (9), steroid+HCQ (16), and no-steroids-no-HCQ (4). The steroid group had reduced large AE and increased SVR as compared to the HCQ group (8.3 mmHg x mL x 10 and 18.4 dyne x sec x 10(-3) versus 13.7 and 14.4, respectively). Mean large AE and the SVR of the HCQ group was similar to that of the controls (11.8 mmHg x mL x 10 and 14.5 dyne x sec x 10(-3), respectively). Mean large AE and SVR of the steroid+HCQ group were better than the steroid group (10.4 mmHg x mL x 10 and 16.0 dyne x sec x 10(-3)). Patients that received steroids had higher rates of hypertension (36%) and diabetes (1%) compared to rest of the patients (15% and 0%, respectively). Small AE, blood pressure, CRP, and SLEDAI were similar between the groups. Among SLE patients, steroid treatment was associated with the highest degree of vascular damage, and HCQ was associated with the lowest degree of vascular damage. It is possible that the steroids are responsible in part to the increased large-vessel manifestations observed in these patients, and that HCQ might have a protective effect on the vessel wall.


Adrenal Cortex Hormones/adverse effects , Antirheumatic Agents/therapeutic use , Hydroxychloroquine/therapeutic use , Lupus Erythematosus, Systemic/drug therapy , Muscle, Smooth, Vascular/drug effects , Arteries/drug effects , Diabetes Mellitus , Elasticity/drug effects , Female , Humans , Hypertension/complications , Lupus Erythematosus, Systemic/complications , Male , Middle Aged , Vascular Resistance/drug effects
16.
Harefuah ; 146(5): 352-3, 406, 2007 May.
Article He | MEDLINE | ID: mdl-17674551

Osteoarthritis (OA) is the most common form of articular disorders, and is primarily a disorder of hyaline cartilage and subchondral bone, although all tissues in and around involved joints are hypertrophic. The etiology of OA is multifactorial, its prevalence is increasing and treatment is focused mainly on pain control and reduction of disability. One of the recently studied treatments, which were found to improve OA, is acupuncture. Acupuncture, a method of Chinese medicine, involves insertion of thin needles into specific points on the body. It was demonstrated in various studies, that acupuncture regulated pro- and anti-inflammatory cytokines, increases the release of neuropeptides and opioids, and regulates vasodilatation. These biological mechanisms can shed a light on the efficacy of acupuncture on various syndromes, including OA. Future research should emphasize the specific acupuncture protocol of treatment best suited for OA (duration and frequency of treatments, specific optimal acupoints for OA and evaluation of acupuncture as adjuvant or as alternative treatment).


Acupuncture , Osteoarthritis/therapy , Humans
17.
Vaccine ; 23(3): 321-4, 2004 Dec 02.
Article En | MEDLINE | ID: mdl-15530675

AIMS: We evaluated the usefulness of skin test prepared by inactivation of vaccinia vaccine in predicting immunity to vaccinia. Skin test was injected to 77 healthy adults. Twenty had a recent smallpox vaccination (group 1). Thirty-seven were long term vacinees (group 2), while 20 subjects had never been vaccinated for smallpox (group 3). RESULTS: Mean size of induration was 7.9, 5.3 and 0.4 mm for subjects from groups 1, 2 and 3, respectively (P<0.03 for difference between groups). Induration >or=5 mm correlated with neutralizing antibody titer >1:32 (r=0.73, P<0.0001). CONCLUSIONS: The skin test is a potentially useful tool for the assessment of immunity to vaccinia.


Smallpox Vaccine/immunology , Smallpox/prevention & control , Vaccinia virus/immunology , Viral Vaccines/immunology , Adolescent , Adult , Antibodies, Viral/blood , Female , Humans , Immunoblotting , Male , Middle Aged , Pharmaceutical Solutions , Skin Tests , Smallpox Vaccine/administration & dosage , Smallpox Vaccine/adverse effects , Time Factors , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/adverse effects , Vaccines, Inactivated/immunology , Viral Vaccines/administration & dosage , Viral Vaccines/adverse effects
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