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Biomedical subjects

G Zandman-Goddard

Publications and source records attributed to G Zandman-Goddard.

At least 19 recordsLinked to original sources
PubMed2005

Anti-serum amyloid component P antibodies in patients with systemic lupus erythematosus correlate with disease activity.

OBJECTIVE: To determine the presence of raised titres of anti-serum amyloid P component (SAP) antibodies in patients with systemic lupus erythematosus (SLE) and to evaluate their correlation with clinical disease by the SLEDAI and clinical manifestations. METHODS: 452 samples were screened for raised anti-SAP antibody titres by an ELISA. Clinical measures and SLEDAI scores were independently reviewed from medical records. 21 serial samples from 7 patients with SLE were assessed for a change in anti-SAP antibody titres after treatment. RESULTS: Raised anti-SAP antibody titres were detected in 145/328 (44%) SLE samples. In 112 randomly selected samples, 69/112 (62%) patients had raised anti-SAP antibodies and anti-dsDNA antibody titres, whereas only 32/112 (28%) had raised anti-dsDNA antibody titres without raised anti-SAP antibody titres. The mean titre of anti-SAP antibodies in patients with active disease was higher than in patients with inactive disease and controls. SLEDAI scores, assessed in 54 patients, were raised in 26/31 (84%) patients with raised anti-SAP antibody titres. A SLEDAI score >or=8 was found in 16/31 (52%) patients with raised anti-SAP antibody titres but in only 5/23 (22%) patients without raised titres. No specific pattern of disease was detected in patients with or without raised titres of anti-SAP antibodies. Serial sampling from patients with active SLE and raised anti-SAP antibody titres showed that anti-SAP antibody titres decreased after treatment and correlated with clinical improvement. CONCLUSION: Raised anti-SAP antibody titres detected in patients with SLE correlate with disease activity and decrease with improvement of clinical disease, and thus may serve as an additional prognostic marker.

Adolescent↗
PubMed2005

Multiplexed AtheNA multi-lyte immunoassay for ANA screening in autoimmune diseases.

BACKGROUND: Multiplexed assays using fluorescence microspheres is an exciting technology with multiple applications including the detection of antinuclear autoantibodies (ANA) and autoantibody profiles. It is a rapid, sensitive and automatic method for simultaneous quantitative detection of several autoantibodies. The aim of our study was to determinate ANA and other autoantibodies to the nine extractable nuclear antigens by the AtheNA Multi-Lyte ANA system and compare the results achieved by this method to the routinely used enzyme immunoassay. METHODS: Four hundred eighteen serum samples were tested utililizing the multiplexed method: 96 healthy donors, 86 requested ANA specimens obtained from routine lab, and 236 samples from patients with known autoimmune diseases (43-scleroderma, 113-systemic lupus erythematosus, 38-Sjogren's syndrome, and 42 rheumatoid arthritis). The ANA and antibodies to nine different analytes (SS/A, SS/B, Sm, RNP, Jo-1, Scl-70, dsDNA, Centromere B and Histone) were tested. RESULTS: ANA screening by AtheNA system revealed high concordance of 99 and 97.7% with the enzyme immunoassay test in samples obtained from healthy donors and ANA requested samples, respectively. Evaluation of autoimmune disease-related samples for ANA by AtheNA technology also confirmed a high rate of concordance of 92-97.7% and correlated with the enzyme immunoassay. Positive discrepant results were found for Scl-70 specificity in 12.7% of SLE specimens by AtheNA technology, while all tested sera were negative for this antibody by enzyme immunoassay. Negative discrepant results were observed by the AtheNA system for anti-dsDNA. The sera (15 randomly obtained samples from SLE patients) were positive for anti-dsDNA in 50% of samples in Farr assay and 55% in enzyme immunoassay, respectively. CONCLUSION: We suggest that the AtheNA technology may be a useful diagnostic tool for ANA screening. Additional investigations are required to compare an analytic performance between AtheNA and routine methods in determination of the individual autoantibody profile.

Antibodies, Antinuclear↗
PubMed2005

The diagnostic utility of anti-cyclic citrullinated peptide antibodies, matrix metalloproteinase-3, rheumatoid factor, erythrocyte sedimentation rate, and C-reactive protein in patients with erosive and non-erosive rheumatoid arthritis.

OBJECTIVE: To compare the diagnostic utility of laboratory variables, including matrix metalloproteinase-3 (MMP-3), anticyclic citrullinated peptide (CCP) antibodies, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) in patients with erosive and non-erosive rheumatoid arthritis (RA). METHODS: We assembled a training set, consisting of 60 patients with RA, all fulfilling the revised criteria of the American College of Rheumatology. A commercial enzyme linked immunosorbent assay (ELISA) was used both to test for anti-CCP antibodies (second generation ELISA kit) and MMP; RF were detected by latex-enhanced immunonephelometric assay. CRP was measured by latex turbidimetric immunoassay. RESULTS: The levels of anti-CCP antibody titers and ESR were significantly higher in patients with erosive disease than those in non-erosive RA patients (p < 0.001 and 0.0341) respectively. Moreover, a higher frequency of elevated titers of anti-CCP antibodies was found in RA patients with erosions compared to patients with non-erosive RA (78.3% vs. 43.2% respectively). The ROC curves of anti-CCP passed closer to the upper left corner than those other markers and area under the curve (AUC) of anti-CCP was significantly larger than AUC of other markers (0.755 for anti-CCP, 0.660 for ESR, 0.611 for CRP, 0.577 for RF, and 0.484 for MMP-3 female). A positive predictive value was higher for anti-CCP antibodies in comparison to other markers. We did not find significant statistical correlation between anti-CCP antibody titers and inflammatory markers such as ESR or CRP. However, we confirmed the correlation of elevated titers of anti-CCP antibodies and RF in both groups of patients whereas the degree of correlation was more significant in non-erosive patients. CONCLUSION: The results of our study suggest that the presence of elevated anti-CCP antibody titers have better diagnostic performance than MMP-3, RF, CRP and ESR in patients with erosive RA.

Aged↗
PubMed2005

Mycophenolate mofetil in animal models of autoimmune disease.

Mycofenolate mofetil (MMF-Cellcept) is an immunomodulatory drug utilized extensively in transplant medicine. The efficacy of regimes including Cellcept in preventing allograft rejection, and in the treatment of rejection, is now firmly established. The immunosuppressive actions of this drug enabled the investigation for the beneficial effects in autoimmune diseases. We review the evidence for the contribution of MMF in autoimmunity in animal models of systemic lupus erythematosus (SLE), mercury induced autoimmune glomerulonephritis, diabetes mellitus, experimental autoimmune uveoretinitis, and experimental allergic encephalitis. MMF has an influence on the T and B cell pathways. It is immunosuppressive and anti-inflammatory.

Animals↗
PubMed2005

Evaluation of the BioPlex 2200 ANA screen: analysis of 510 healthy subjects: incidence of natural/predictive autoantibodies.

The BioPlex 2200 ANA Screen is a fully automated system that determines levels for 13 different autoimmune antibodies of established clinical significance. The objective of this study was to determine the specificity of the BioPlex 2200 ANA Screen assay and to analyze the antibody profile samples collected from healthy subjects against comparative ELISA and IIF screening methods. A total of 510 specimens were randomly selected from a cohort of apparently healthy blood bank donors. Samples were distributed to five age brackets. All samples were tested using Bio-Rad's ANA Screen kit. Specificity was compared to IIF and ELISA results. Most of the samples were found negative in all ANA screening systems (84.5% by IIF, 92.5% by BioPlex 2200 ANA Screen kit, and 94.5% by ELISA). The frequency of positive results was highest (15.5%) using IIF, in comparison to almost similar results (5.5% vs. 7.5%) achieved by ANA ELISA and BioPlex 2200 ANA Screen kits. The positive rate of autoantibodies was significantly reduced when analyzed by different combinations of ANA screen assays (from 2.35% using IIF + BioPlex ANA Screen tests to 0.98% by using all three tests). Using the BioPlex 2200 ANA Screen system, we were able to identify samples with high levels of individual antibodies: anti-dsDNA at 20-63 IU/mL, antichromatin at 4-8 AI, anti-SmRNP at 2-6 AI, and anti-RNPA at 2-4.5 AI. Importantly, from 7 IIF and ELISA positive sera, 5 of these were also BioPlex 2200 positive, suggesting that the BioPlex is seeing the samples that are of the greatest interest, using the established techniques. The specificity of the BioPlex 2200 ANA Screen analysis of 13 different analytes (dsDNA, centromere B, chromatin, Jo1, ribosomal P, RNP 68, RNP A, Scl-70, Sm, SmPNP, SS-A52, SS-A60, SS-B) is comparable (P < 0.252) to the ELISA ANA screening test. Like the ELISA, the BioPlex 2200 has a lower (P < 0.001) positive rate than IIF for the autoantibody screening.

Age Distribution↗
PubMed2004

The systemic nature of the antiphospholipid syndrome.

Antiphospholipid syndrome (APS, Hughes' syndrome) is a systemic autoimmune disorder characterized by arterial and/or venous thrombosis and recurrent foetal loss, accompanied by mild to moderate thrombocytopaenia and elevated titres of antiphospholipid antibodies (aPLs): lupus anticoagulant (LAC) and/or anticardiolipin (aCL) antibodies. APS was defined originally in 1983 in systemic lupus erythematosus (SLE) patients, but later it was found that APS can be primary or secondary to other autoimmune diseases or malignancy. During the past 20 years many organs have been reported to be involved in this syndrome and the clinical manifestations are seen in every medical field. Moreover, many aPLs have been found in APS besides aCLs and LACs, which bind to the autoantigen beta-2-glycoprotein I (beta2GPI). Treatment for APS, based on antiplatelet and anticoagulation drugs, is dependent on various parameters, including whether SLE is also present, classical vs non-classical manifestations of the diseases, women with APS based on pregnancy morbidity, the presence of elevated aCL antibody titres in the absence of clinical manifestations, and catastrophic APS.

Antibodies, Anticardiolipin↗
PubMed2003

10th International Congress on Antiphospholipid Antibodies--summary.

The 10th International Congress on Antiphospholipid Antibodies (Sicily, Italy, September 29-October 3, 2002) (Fig. 1) provided enlightening aspects on the recent developments in antiphospholipid syndrome (APS) and antiphospholipid antibodies in more than 150 lectures and posters. Researchers from all aspects of medicine attended the meeting, implicating the systemic characteristics of APS. The important breakthroughs are summarized.

Animals↗
PubMed2002

Combined autoimmune disease in a patient with AIDS.

Immune dysregulation in HIV-infected patients, along with the new medications for treatment of AIDS that possess immunomodulating potential, may lead to an increased incidence of autoimmune diseases in this patient population. However, the presence of combined autoimmune diseases in an AIDS patient is rare. Relapsing polychondritis (RP) is an uncommon inflammatory disease manifested by recurrent attacks of auricular chondritis. The presence of type II and IX collagen antibodies, and their association with HLA-DR4 and other autoimmune diseases, suggests that antiself reactions may be present. Sarcoidosis is a granulomatous disease manifested by inflammation of the lungs, eyes and joints. In the peripheral blood there is depressed cellular immunity and enhanced humoral immunity. We here describe a case of coexisting RP and sarcoidosis in an AIDS patient.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Antiphospholipid syndrome induced by HIV.

A 24-y-old male who developed necrotic lesions on the lower extremities together with testicular thrombosis necessitating orchiectomy, demonstrated high level IgG anticardiolipin (aCL) associated with acute HIV infection. This is one of the first cases describing a close relationship between viral infection and the classic antiphospholipid syndrome (APS). It is well documented that HIV patients may produce antiphospholipid antibodies (aPL), but the full-blown picture of the APS is distinctly uncommon with HIV or any other viral infection, possibly due to the overproduction of the IgM isotype rather than IgG aCL as in this case. The induction of thrombosis following infections has been well described in patients with catastrophic antiphospholipid syndrome (CAPS) but not in patients with the 'classic or simple' APS.

Adult↗
PubMed2001

[The lack of awareness of the Israeli population regarding gastrointestinal complications from non-steroidal anti-inflammatory drugs].

Non-steroidal anti-inflammatory drugs (NSAID) are potent analgesic agents. They are indicated for rheumatoid arthritis, osteoarthritis, severe acute and prolonged chronic pain. A wide range of analgesic agents are available. The objective of this study was to assess the patient's knowledge of his illness, his knowledge familiarity with NSAID medications and their side effects and thereupon, to evaluate the awareness, utilization, satisfaction and expectations associated with current available treatment. During the year 2000, a randomized telephone screening questionnaire, was completed over a 2 month period for a sample group of the general Israeli population over 50 years of age. Of the 3179 persons contacted, 2028 responded and 292 persons were treated with NSAIDs and further investigated. Fifty percent suffered from chronic musculoskeletal pain, 22% had osteoarthritis, 10% had rheumatoid arthritis, and 18% had undefined chronic pain. The average age of the respondent was 65 years old. The average duration of treatment was 11 years. The most common drugs used by the 292 respondents that were taking NSAIDs were diclofenac (Voltaren)--51% and naproxen (Naxyn)--21%. Only 4% were treated with COX-2 specific inhibitors. Twenty percent of the respondents utilized more than one NSAID simultaneously. Forty seven percent of the patients had peptic ulcer disease but only 39% of them were simultaneously treated with an NSAID and a gastroprotective agent. Sixty eight percent of patients expected amelioration of symptoms while taking NSAIDs. Seventy seven percent of respondents were dissatisfied with treatment. The patients expressed that they did not have a reliable easily accessible source of information on their disorder or on available treatment options. Many respondents were not aware of their medical diagnosis. In general, patients were not aware of all the available NSAIDs or the side effects of gastrointestinal complications. Enhancement of information available to the patient is warranted to improve the provision of efficient therapy, reduce side effects and increase patient satisfaction from therapy.

Aged↗
PubMed2000

Novel approaches to therapy for systemic lupus erythematosus.

Current therapies for systemic lupus erythematosus (SLE) are targeted at immunosuppression and at reducing inflammation. The current therapies are broad-spectrum and include steroids and cytotoxic agents that are counterbalanced by toxicity and side effects of the medications. Methotrexate can be utilized to reduce steroid requirements in mild to moderate SLE. Manipulation of the hormonal axis includes DHEA and bromocriptine. Mycophenolate mofetil is an immunosuppressive agent that is being investigated for SLE renal disease. Autologous stem cell transplantation or high-dose cyclophosphamide may be an option for severe refractory SLE. The aim of the future is to target therapies by altering specific known mechanisms of inflammation and autoimmunity. Although the inciting antigen is still unknown in SLE, it may be possible to alter the regulation of the immune response by targeted molecular therapy. Methods to do so would include manipulation of idiotypes, manipulation of second signal stimulation of the immune response, manipulation of cytokines, and the induction of tolerance by administration of blocking peptides. IVIg is an immunomodulator that has been successful in the treatment of SLE. Targeted molecular therapy is undergoing phase I trials with monoclonal anti-CD40L, a signaling inhibitor. Anti-CTLA4Ig, another signaling blocker, is presently being investigated for psoriasis, but may be a potential therapy for SLE. Finally, therapies may include the administration of peptides to induce tolerance.

Journal Article↗
PubMed1999

A comparison of autoantibody production in asymptomatic and symptomatic women with silicone breast implants.

OBJECTIVE: We previously reported an increased preponderance of a broad range of autoantibodies in symptomatic women with silicone breast implants. The objective of this study was to investigate the frequency of autoantibody production in asymptomatic compared to symptomatic women with silicone implants. One hundred twenty-two asymptomatic women were recruited to our center for autoantibody detection through an advocate dealing with breast implant liabilities. METHODS: Autoantibody detection in 86 asymptomatic women was done blindly on a panel of 15 different antibodies (dsDNA, ssDNA, histones, SSA/Ro, SSB/La, RNP, cardiolipin, phosphatidylserine, pyruvate dehydrogenase, Scl-70, NC-1, silicone, collagen I, II, and IV). Clinical variables, specific questioning about related silicone implant symptoms, and a rheumatological examination were performed blindly by a certified rheumatologist. The findings were recorded and at a later stage compared with positive autoantibody detection. The normal control group consisted of age and sex matched Israeli women without known autoimmune disease. In the positive control group were symptomatic women previously tested for antibody production. The autoantibodies were assessed by ELISA. Values from individual patients were considered positive only when greater than 3 standard deviations above the control mean. RESULTS: The mean ages of 86 asymptomatic and 116 symptomatic women were 46.2+/-11.2 and 45.7+/-8.3 years, respectively. Breast implants were in place for a mean period of 8.2+/-5.0 years in the asymptomatic group and 15.0+/-5.6 years in the symptomatic group. The incidence of increased titers of autoantibodies ranged from 2 to 13% for 13 different autoantibodies among asymptomatic women. Among symptomatic women, 20% harbored 4 autoantibodies and 8% had 6 autoantibodies. The most common antibodies in the asymptomatic group were: dsDNA 8%; ssDNA 9%; SSB/La 13%; silicone 9%; collagen II 9%. No autoantibodies were found for NC-1, Scl-70, or RNP. Among the symptomatic group, the most common autoantibodies were histone ribosomal phosphate, SSA, SSB, Scl-70, cardiolipin, phosphatidylserine, GM2-ganglioside, and NC-1. Comparison of autoantibody incidence in asymptomatic and symptomatic women with silicone breast implants revealed an increased incidence of anti-SSB/La and anticollagen II in both groups. Polyclonality was more prominent in the group of symptomatic women with silicone breast implants, but also evident in 3 asymptomatic women. CONCLUSION: The mean duration of implant in the asymptomatic group was significantly less compared with the symptomatic group (p<0.01). The development of autoantibodies may be related to implant duration.

Adult↗
PubMed1997

Lupus-specific antibodies reveal an altered pattern of somatic mutation.

The F4 idiotype is a heavy chain determinant expressed almost exclusively on IgG immunoglobulins and is highly associated with specificity for double-stranded DNA. Since high-titered F4 expression is present predominantly in sera of patients with systemic lupus erythematosus (SLE), we thought F4+ IgG antibodies might constitute a useful subset of immunoglobulins in which to investigate lupus-specific alterations in variable (V) region gene expression or in the process of somatic mutation. This molecular analysis of F4+ B cell lines generated from lupus patients demonstrates that despite the strong association of F4 reactivity with specificity for native DNA, there is no apparent VH gene restriction. Furthermore, VH gene segments encoding these antibodies are also used in protective immune responses. An examination of the process of somatic mutation in F4+ antibodies showed no abnormality in frequency of somatic mutation nor in the distribution of mutations in complementarity-determining regions or framework regions. However, there was a decrease in targeting of mutations to putative mutational hot spots. This subtle difference in mutations present in these antibodies may reflect an intrinsic defect in mutational machinery or, more likely, altered state of B cell activation that affects the mutational process and perhaps also negative selection.

Amino Acid Sequence↗
PubMed1997

Successful treatment of early secondary myelofibrosis in SLE with IVIG.

Myelofibrosis has been reported as a rare cause of pancytopenia in patients with autoimmune diseases. We describe a 54y old female patient who was admitted with severe anemia subsequently found to be due to marrow fibrosis. During the course of her hospitalization, relying both on her clinical symptoms as well as the results of a wide range of laboratory tests and diagnostic procedures, the diagnosis of systemic lupus erythematosus was established. The patient was treated with high dose steroids, but improvement of her clinical symptoms as well as normalization of her peripheral blood count were achieved only after high dose intravenous therapy with gamma globulin (IVIG) was instituted. Along with the improvement in the peripheral blood parameters normalization of the bone marrow architecture was recorded on a repeated bone marrow biopsy. IVIG therapy should be considered in extreme cases of bone marrow suppression in SLE.

Biopsy↗
PubMed1996

The effects of early and late administration of M-20 derived interleukin-1 inhibitor on experimental systemic lupus erythematosus.

M-20 interleukin-1 inhibitor is produced by a myelomonocytic cell line. The effects of this molecule, mediated via IL-1 inhibition, include decreased proliferative responses of mouse thymocytes, human T-cells and fibroblasts and reduction in parameters of acute inflammation. Previously, we have demonstrated the emergence of a disease resembling systemic lupus erythematosus (SLE) in naive mice immunized with anti-DNA antibodies carrying different pathogenic idiotypes. The disease was manifested by increased titers of various mouse antibodies, concomitant with the appearance of elevated erythrocyte sedimentation rate (ESR), proteinuria and leukopenia. We have applied this model of experimental SLE (immunized with MIV-7, a human monoclonal antibody) to evaluate the influence of M-20 IL-1 inhibitor, administered at different stages (2 weeks before, 1 month and 3 months following immunization) for a period of 2 weeks, on the findings of the disease in mice. It was shown that M-20 IL-1 inhibitor given 2 weeks prior to the immunization resulted in suppression of the disease induction as documented by lower antibody titer level (30%-50% in the immunized mice as compared with controls). Furthermore, reduced autoantibody levels were accompanied by other beneficial findings consisting of lower ESR, less severe proteinuria and elevated leukocyte counts. No beneficial effects of M-20 IL-1 inhibitor were observed when the agent was administered 1 or 3 months following immunization. We conclude that M-20 IL-1 inhibitor has a favorable effect on experimental SLE in mice, provided it is administered before induction of the disease.

Animals↗
PubMed1996

Modulation of experimental systemic lupus erythematosus with linomide.

OBJECTIVE: The objective of this study was to assess the beneficial effects of an early administration of low dose linomide, a new immunomodulator, in an animal model of experimental systemic lupus erythematosus (SLE). METHODS: Experimental SLE was induced in naive BALB/c mice, by immunization with anti-DNA mAb (MIV-7). Control Mice immunized with irrelevant human IgM served as controls. The immunized mice were treated with linomide (0.1 mg/ml in the drinking water), four weeks prior to the first immunization, at an early stage of the disease induction (one month after boost injection), or at a later stage (3 months following boost immunization). The treatment duration was 3 months in all schedules. The follow-up studies continued for 8 weeks after discontinuation of the treatment. The presence in the serum of autoantibodies against ssDNA, dsDNA histones, phospholipids and an irrelevant autoantigen-pyruvate dehydrogenase, was determined by enzyme-linked immunosorbent assay (ELISA). The clinical parameters assessed included erythrocyte sedimentation rate, peripheral blood cell counts and proteinuria. RESULTS: There was a 50-64% decrease in autoantibody levels in the sera of mice immunized with anti-DNA (MIV-7) mAb at the early stage of experimental SLE in mice which received linomide for a period of 3 months. No effect of linomide was noted in mice which received the drug during the later stages of experimental SLE when the disease was fully developed. Linomide had a preventive effect on the induction of experimental SLE in naive mice, when the treatment was initiated before the induction of the disease. This effect was abolished following cessation of the treatment. CONCLUSIONS: Linomide proved to be effective at the early stages of induction of the experimental SLE. However, the autoantibody levels rose following discontinuation of the therapy.

Adjuvants, Immunologic↗
PubMed1995

Systemic lupus erythematosus and thymoma--a double-edged sword.

The coexistence of systemic lupus erythematosus (SLE) and thymoma is rare. We describe 2 female patients with this combination. A 48-year-old woman presented with dyspnea due to a left pleural effusion. Her past history revealed over the previous 3 years the development of anemia, thrombocytopenia, alopecia, pericardial effusion and proteinuria. Four months prior to this hospitalization, the patient was first admitted due to purpura. At that time, laboratory tests revealed an elevated sedimentation rate, elevated titers of ANA and anti-DNA. Chest X-ray demonstrated a widened mediastinum, and upon operation an encapsulated thymoma was excised. Four months following the thymectomy, the patient is unresponsive despite high dose steroid therapy. Another patient, a 30-year-old woman, presented with SLE (cutaneous, arthritis, anemia, positive ANA and high titers of anti-DNA) and thymoma simultaneously. Six years after thymectomy the patient is in SLE remission. Thymectomy in mice prone to autoimmunity (NZB/W mice) has been shown to accelerate the autoimmune manifestations. Conversely, the opposite effect is seen in MRL/lpr mice. The immunological effect of adult thymectomy on the course of human SLE remains to be established, on a larger series of patients. It seems that the heterogenicity of human patients is exemplified by the contrasting effects of thymectomy for thymoma in SLE patients.

Adult↗