[Safety of specific cyclo-oxygenase 2 inhibitors].
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Animals↗
Biomedical subjects
A J Swaak
Publications and source records attributed to A J Swaak.
Incomplete lupus erythematosus: results of a multicentre study under the supervision of the EULAR Standing Committee on International Clinical Studies Including Therapeutic Trials (ESCISIT).
OBJECTIVE: Patients characterized with antinuclear antibodies (ANA) and disease symptoms related to one organ system can be described as having incomplete systemic lupus erythematosus (SLE). The aim of this multicentre study was to describe the outcome of these so-called incomplete SLE patients. Two aspects of the outcome were studied: (i) the disease course, defined by the presence or absence of clinical symptoms; and (ii) the number of patients that eventually developed full SLE. METHODS: Outcome parameters were the ACR criteria, the SLE disease Activity Index (SLEDAI), the European Consensus Lupus Activity Measure (ECLAM) and the requirement for treatment. In 10 European rheumatology centres, patients who had been evaluated in the last 3 months of 1994 and had been diagnosed as having incomplete SLE on clinical grounds for at least 1 yr were included in the study. All 122 patients who were included in the study were evaluated annually during 3 yr of follow-up. RESULTS: Our results are confined to a patient cohort defined by disease duration of at least 1 yr, being under clinical care at the different centres in Europe. These patients showed disease activity that was related mostly to symptoms of the skin and the musculoskeletal system, and leucocytopenia. During the follow-up, low doses of prednisolone were still being prescribed in 43% of the patients. On recruitment to the study, 22 of the 122 incomplete SLE patients already fulfilled the ACR criteria for the diagnosis of SLE. In the 3 yr of follow-up only three patients developed SLE. CONCLUSIONS: A high proportion of patients in our cohort defined on clinical grounds as having incomplete SLE eventually showed disease activity defined by the SLEDAI as well as ECLAM. However, only three cases developed to SLE during the follow-up. This suggests that incomplete SLE forms a subgroup of SLE that has a good prognosis.
Adolescent↗
Systemic lupus erythematosus. Disease outcome in patients with a disease duration of at least 10 years: second evaluation.
Data related to the disease course of patients with systemic lupus erythematosus (SLE) with special attention to the persistence of disease activity in the long term are scarce. At this moment reliable figures are only known about the survival rate as a measure of outcome. The aim of this multicenter study was to describe the outcome of SLE patients with a disease duration of greater than 10 y. Outcome parameters were two disease activity-scoring systems (SLEDAI and ECLAM), the end organ damage (SLICC/ACR damage index) and treatment. Our results are derived from 187 SLE patients followed at 10 different centres in Europe over a period of 1 y. Serious clinical signs or exacerbations, defined by the occurrence or detoriation of already existing symptoms of renal and cerebral nervous systems were observed in 2-11% of the patients, seizures and psychosis in 3%, proteinuria in 11% and an increase in serum creatinine in 5% of the patients. No change took place in the overall damage index. Yet, the disease course in most patients was characterized by periods of tiredness (42-60%), arthritis (20-25%), skin involvement such as malar rash (32-40%), migraine (15-20%), anaemia (15%) and leucopenia (17-19%). Summarizing these results it is shown that patients, still under care after such a long time of having this disease, do have a disease that is far from extinguished.
Adult↗
[Diagnostic significance of antinuclear antibodies].
In three patients, women of 17, 25 and 15 years, suffering from arthralgia and in whom the existence of antinuclear antibodies (ANA) was established, the diagnosis 'systemic lupus erythematosus' was made or considered. Upon reevaluation, the ANA results could not be confirmed. The conclusion was drawn that in patients, who lack one or more clinical signs of a connective tissue disease (CTD), no indication is present for determination of ANA. Literature data indicate that the positive predictive value of ANA for the presence of CTD is 5-10%. Conversely, a negative ANA result does not rule out that CTD is present (negative predictive value: 98.5-99.3%). In addition, the question is raised if a hospital laboratory, lacking experience or routine in ANA assays could reliably perform these assays.
Acute Disease↗
Histone-containing immune complexes are to a large extent responsible for anti-dsDNA reactivity in the Farr assay of active SLE patients.
Increased titres of anti-dsDNA antibodies, especially if of high avidity, are associated with renal exacerbations in patients with systemic lupus erythematosus (SLE). One of the most reliable assays to measure anti-dsDNA antibodies, the Farr assay, is believed to detect preferentially high avidity antibodies. Purified non-complexed monoclonal antibodies (mAbs) against nucleosomes, obtained from mice with SLE, are not reactive in the Farr assay, but can become so once complexed to nucleosomes. These Farr-positive, nucleosome containing, immune complexes were also able to bind in vivo to the glomerular basement membrane (GBM), predominantly via heparan sulphate (HS). To evaluate whether in SLE patients the same kind of immune complexes are responsible for Farr reactivity, IgG from serum or plasma was isolated under dissociating and physiological conditions. We observed that after purification under dissociating conditions, Farr reactivity was significantly decreased (P<0.0001) in contrast to reactivity with histones and two 'control' antigens: Epstein Barr Virus (EBV) and Ro/SS-A. Reactivity with nucleosomes also decreased after purification, although to a lesser extent. Plasma purified under physiological conditions showed no decrease in Farr reactivity. The importance of histones for the generation of immune complexes is supported by the two following observations. Firstly, the presence of histones could be demonstrated in serum and plasma of SLE patients but not in serum of healthy controls or in IgG preparations purified under dissociating conditions. Secondly, Farr reactivity of purified IgG preparations could be restored by addition of purified histones. From these studies we conclude that histones containing immune complexes are responsible for a large part of the Farr reactivity in active SLE, and are therefore indirectly implicated in the pathogenesis of lupus nephritis.
Animals↗
First evaluation study of the Dutch Working Party on silicone breast implants (SBI) and the silicone-related symptom complex (SRSC).
This cohort study evaluates the postoperative prevalence of antinuclear antibodies (ANA) in relation to symptoms related to the so-called silicone-related symptom complex (SRSC). A total of 63 women who underwent mastectomy followed by immediate breast reconstruction with a silicone implant (SBI) between Septembber 1990 and May 1995 at the University Hospital Rotterdam/Daniel den Hoed Cancer Center, participated voluntarily in the study. Their sera were tested for the presence of antinuclear antibodies (ANA) and at the same time they were screened for the prevalence of SRSC-related symptoms by questionnaire. All patients were also examined physically. Sixteen per cent of the women were ANA positive. There was no difference in SRSC expression between ANA-positive and ANA-negative women. The lack of difference in symptom expression between the ANA-positive and ANA-negative women and the rather low complaint percentage proves that if ANA positivity is related to the SRSC, we found no evidence that patients with a SBI with a positive ANA differed from the ANA-negative patients.
Adult↗
Systemic toxicity and cytokine/acute phase protein levels in patients after isolated limb perfusion with tumor necrosis factor-alpha complicated by high leakage.
BACKGROUND: Since the introduction of high-dose tumor necrosis factor-alpha (TNFalpha) in the setting of isolated limb perfusion (ILP) in the clinic, prevention of leakage to the body of the patient is monitored with great precision for fear of TNF-mediated toxicity. That we observed remarkably little toxicity in patients with and without leakage prompted us to determine patterns of cytokines and acute phase proteins in patients with high leakage and in patients without any leakage. METHODS: TNFalpha, interleukin (IL)-6, IL-8, C-reactive protein, and secretory (s)-phospholipase A2 were measured at several time points during and after (until 7 days) ILP in 10 patients with a leakage to the systemic circulation varying in percentage from 12% to 65%. As a control, the same measurements, both in peripheral blood and in perfusate, were performed in nine patients without systemic leakage. RESULTS: In patients with systemic leakage, levels of TNFalpha increased during ILP, reaching values to 277 ng/ml. IL-6 and IL-8 peaked 3 hours after ILP with values significantly higher compared with patients without systemic leakage. C-reactive protein and s-phospholipase A2 peaked at day 1 in both patient groups, s-phospholipase A2 with significant higher levels and C-reactive protein, in contrast, with lower levels in the leakage patients. CONCLUSIONS: High leakage of TNFalpha to the systemic circulation, caused by a complicated ILP, led to 10-fold to more than 100-fold increased levels of TNFalpha, IL-6, and IL-8 in comparison with patients without leakage. The increase of the acute phase proteins was limited. Even when high leakage occurs, this procedure should not lead to fatal complications. The most prominent clinical toxicity was hypotension (grade III in four patients), which was easily corrected. No pulmonary or renal toxicity was observed in any patient. It is our experience that, even in the rare event of significant leakage during a TNFa-based ILP, postoperative toxicity is usually mild and can be easily managed by the use of fluid and, in some cases, vasopressors.
Acute-Phase Proteins↗
Intrapleural administration of tumour necrosis factor-alpha (TNFalpha) in patients with mesothelioma: cytokine patterns and acute-phase protein response.
BACKGROUND: Tumour necrosis factor-alpha (TNFalpha) has been found to be very effective in the isolated limb perfusion setting for advanced extremity tumours. In a phase I study of intrapleural administration of TNFalpha 5 patients were followed for inflammatory response patterns. PATIENTS AND METHODS: Malignant mesothelioma patients were treated with repeated intrapleural administration of 0. 1-0.2 mg recombinant TNFalpha. Samples of serum and pleural fluid were taken at different time-points before and after TNFalpha-administration. Levels of TNFalpha, interleukin-6 (IL-6), interleukin-8 (IL-8), C-reactive protein (CRP) and secretory phospholipase A2 (sPLA2) were measured using enzyme-linked immunosorbent assays (ELISAs). Alpha 1-acid glycoprotein (alpha1-AG) was measured by nephelometry. RESULTS: In pleural fluid TNFalpha and IL-8 reached peak levels, up to 50-700 ng mL-1 and 6-60 ng mL-1, respectively, 24 h after administration of TNFalpha. IL-6 (peak levels up to 250 ng mL-1) and sPLA2 peaked after 48 h. A slower and less dramatic pattern was observed for the levels of CRP and alpha1-AG. In serum no detectable levels of TNFalpha and no IL-8 were observed, whereas serum levels of IL-6, sPLA2 and CRP showed a clear increase after intrapleural administration of TNFalpha. Cytokines and acute-phase proteins showed the same pattern during subsequent cycles even up to 12 cycles. Tumour regression was not observed. CONCLUSIONS: In the setting of a phase I study of repetitive intrapleural administration of TNFalpha in mesothelioma patients, we studied the characteristics of the inflammatory response. Intrapleural administration was followed by a clear inflammatory response locoregionally. In spite of TNFalpha peak levels as high as 700 ng mL-1 systemic levels were never detectable. The secondary cytokine response led to very high intrapleural IL-6 and IL-8 levels. Systemically IL-8 levels were never detectable whereas high IL-6 levels were induced systemically initially, with a decreased response to each intrapleural TNFalpha administration over time. The acute-phase response in contrast remained remarkably constant throughout the course of repeated intrapleural administrations of TNFalpha. Intrapleural administration of TNFalpha is well tolerated but associated with inconsistent and rather moderate impact on production of pleural fluid. This can be achieved by other simpler and cheaper treatment, thus we see no justification for further studies.
Acute-Phase Proteins↗
Recombinant human erythropoietin improves health-related quality of life in patients with rheumatoid arthritis and anaemia of chronic disease; utility measures correlate strongly with disease activity measures.
Treatment with recombinant human erythropoietin (r-hu-Epo) in patients with rheumatoid arthritis (RA) and anaemia of chronic disease (ACD) resulted in improvement of both anaemia and disease activity. Utilities represent a generic and comprehensive quality of life measure, capable of integrating domain-specific information into one overall value which a patient assigns to his state of health. Therefore, the effect of r-hu-Epo on quality of life was studied by measuring utilities, derived from the rating scale and standard gamble, in a 52-week placebo-controlled randomised double-blind study with r-hu-Epo in 70 patients with active RA and ACD. Furthermore, the relation between anaemia as assessed by haemoglobin levels (Hb), disease activity as assessed with the Disease Activity Score (DAS), and utilities was investigated. Compared to the placebo group, significant improvement of Hb (P < 0.001), DAS (P = 0.01) and rating scale utilities (P = 0.002), but not of standard gamble utilities, was observed in the Epo group. Rating scale utilities correlated strongly with DAS (r = -0.47, P < 0.01), Hb (r = 0.37, P < 0.01) and changes in both DAS (r = -0.74, P < 0.01) and Hb (r = 0.44, P < 0.01). Both DAS and Hb contributed significantly to the variance in rating scale utilities (21% and 3% respectively) and to changes in rating scale utilities (43% and 3% respectively). Standard gamble utilities correlated less well with clinical disease variables than rating scale utilities did. These results indicate, that r-hu-Epo improves utility-derived health-related quality of life, most probably by improving both disease activity and anaemia. Utilities, particularly rating scale utilities, correlated well with conventional disease activity variables and proved sensitive to change. Utilities may be a useful tool for investigating quality of life in RA-patients.
Adult↗
Absence of severe systemic toxicity after leakage-controlled isolated limb perfusion with tumor necrosis factor-alpha and melphalan.
BACKGROUND: Severe systemic toxicity and hemodynamic changes after isolated limb perfusion (ILP) with tumor necrosis factor-alpha (TNF-alpha) and melphalan, with or without interferon-gamma, have been reported in several series. We studied whether these side effects could be precluded by preventing leakage from the isolated circuit into the systemic circulation. METHODS: Clinical and pharmacokinetic data for 20 consecutive patients with recurrent melanoma of the limbs who were treated by ILP with TNF-alpha (3-4 mg) and melphalan, with or without interferon-gamma, were studied. Leakage rates and TNF-alpha levels were determined during and after ILP and were correlated with systemic toxicity and hemodynamic changes. RESULTS: Only two patients experienced leaks (2% and 13%) during ILP. For 18 patients without leakage, the mean peak systemic TNF-alpha level was 2.8 ng/ml at 10 minutes after ILP. After leakage, the peak systemic TNF-alpha levels were 31.9 and 88.3 ng/ml at 5 minutes. Toxicity was mild and consisted mainly of fever (n = 17) and nausea/vomiting (n = 19) during the first day after ILP. Some patients developed tachycardia (n = 6), hypotension (n = 3; responding immediately to fluid challenge), a decrease in the WBC count (n = 3; grade I) or thrombocyte count (n = 11; grade I/II, no hemorrhage or therapeutic intervention), or hepatotoxicity [cytolysis (n = 15; 14 grade I/II and 1 grade IV) or hyperbilirubinemia (n = 7; grade I/II, all resolving spontaneously)]. Patients with tachycardia or hepatotoxicity exhibited significantly higher TNF-alpha levels after ILP, compared with other patients. CONCLUSIONS: Systemic toxicity after ILP with TNF-alpha is minimal and does not differ from that after ILP with melphalan alone when leakage is adequately controlled.
Adult↗
Characteristics of recovery from the euthyroid sick syndrome induced by tumor necrosis factor alpha in cancer patients.
Cytokines have been implicated in the pathogenesis of the euthyroid sick syndrome. Isolated limb perfusion (ILP) with recombinant human tumor necrosis factor alpha (rTNF) and melphalan in patients with melanoma or sarcoma is accompanied by high systemic TNF levels. We examined the prolonged effects (7 days) of ILP on thyroid hormone metabolism with respect to induction and recovery of the euthyroid sick syndrome in six cancer patients. After ILP, when the limb is reconnected to the systemic circulation, leakage of residual rTNF resulted in systemic peak levels at 10 minutes postperfusion followed by a parallel increase in plasma interleukin-6 (IL-6) and cortisol, with maximum levels at 4 hours (P < .05). A rapid decrease was observed at 5 minutes for plasma triiodothyronine (T3), reverse T3 (rT3), thyroxine (T4), and thyroxine-binding globulin (TBG) (P < .05), whereas free T4 (FT4) and T3-uptake showed a sharp increase, with peak levels at 5 minutes (P < .05). T3, T4, and TBG levels remained low until 24 hours after ILP In contrast, rT3 increased above pretreatment values to maximum levels at 24 hours (P < .05). Plasma thyrotropin (TSH) showed an initial decrease at 4 hours postperfusion (P < .05) but exceeded pretreatment values from day 1 to day 7 (by +94%+/-43% to +155%+/-66%, P < .05), preceding the recovery of T4 and T3 levels. T3 and rT3 returned to initial values at day 4. T4 and TBG levels recovered at day 2. T4 exceeded basal values at days 5 to 7 (P < .05). It is concluded that ILP with rTNF induces a euthyroid sick syndrome either directly or indirectly through other mediators such as IL-6 or cortisol. The recovery from this euthyroid sick syndrome is, at least in part, TSH-dependent, since the prolonged elevation of TSH values preceded and persisted during the normalization of T3 and the elevation of T4 levels. This biphasic pattern of induction of and recovery from the euthyroid sick syndrome may be a general feature of nonthyroidal disease. The euthyroid sick syndrome should be interpreted not only in relation to the presence of nonthyroidal diseases but also in relation to the recovery from these diseases.
Aged↗
Effects of tumour necrosis factor alpha and melphalan on the cytokine production of circulating T cells in patients with cancer.
BACKGROUND: The objective of the present study was to investigate the effects of isolated limb perfusion (ILP) with tumour necrosis factor alpha (TNF-alpha) and melphalan on circulating T cells from cancer patients using two different methods. DESIGN: Eight patients undergoing an ILP entered the study. At first, the number of T cells at several time points was determined using FACScan. Subsequently, production of interferon gamma (IFN-gamma) (T-helper 1) and interleukin (IL) 4 (T-helper 2) was measured at the intracytoplasmic level after stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin. IFN-gamma, IL-4 and IL-2 (also T-helper 1) production in the whole-blood cell culture system was then determined after stimulation with a combination of anti-CD3/anti-CD28 monoclonal antibodies. RESULTS: An enormous decrease in the number of circulating T cells was observed. In the remaining T-cell population cytokine production (IL-2, IL-4, IFN-gamma) was depressed, showing the same pattern in both methods. No difference could be detected between the effect of TNF-alpha and melphalan on Th1 cells and Th2 cells. CONCLUSIONS: The results demonstrate that TNF-alpha and melphalan reduce the number of circulating T cells and at the single-cell level decrease cytokine production in the remaining circulating T cells. No selective effect of TNF-alpha on Th1 or Th2 cells could be detected. If the impaired T-cell function is representative of all T cells remaining in the systemic circulation, this could help to explain the tolerability of high TNF concentrations after ILP, perhaps by decreasing the synthesis and production of T-cell-derived cytokines.
Adult↗
Acute-phase response patterns in isolated hepatic perfusion with tumour necrosis factor alpha (TNF-alpha) and melphalan in patients with colorectal liver metastases.
BACKGROUND: In this study, we have evaluated hepatotoxicity, secondary cytokine production and hepatic acute-phase response (APR) in patients who underwent isolated hepatic perfusion (IHP) with tumour necrosis factor (TNF) alpha and melphalan for irresectable colorectal liver metastases. DESIGN: An extracorporeal veno-venous bypass was used to shunt blood from the lower body and intestines to the heart. Inflow catheters were placed in the hepatic artery and portal vein, and an outflow catheter in the inferior caval vein. The liver was perfused for 60 min with 0.4 mg of TNF-alpha plus 1 mg kg-1 melphalan (IHPTM group, n = 6) or 1 mg kg-1 melphalan (IHPM group, n = 3). The liver was washed with macrodex before restoring vascular continuity. RESULTS: After the washout procedure, a TNF-alpha peak (169 +/- 38 pg mL-1) was demonstrated in the IHPTM group only. Both groups demonstrated peak levels of interleukin 6 (IL-6) in the perfusate as well as systemically. These were significantly higher in the IHPTM group. Acute-phase protein (APP) levels followed a similar pattern as has been demonstrated after major surgery, with no significant differences between both groups. The addition of TNF-alpha to the perfusate did not lead to a significant difference in APP levels and the time course between groups. CONCLUSIONS: IHP with TNF and melphalan is followed by a transient systemic peak of TNF directly after liver washout. Secondary IL-6 induction was seen in the present study after IHP with and without TNF, which was highest when TNF was added. This phenomenon cannot be extrapolated to APP induction, which appeared unaffected by the addition of TNF, presumably because the surgical procedure itself already causes maximal stimulation of APP production.
Acute-Phase Proteins↗
The prognosis and outcome of patients referred to an outpatient clinic for rheumatic diseases characterized by the presence of antinuclear antibodies (ANA).
To evaluate if patients with symptoms related to the musculoskeletal system, characterized by the presence of ANA, are prone to develop SLE or other specific rheumatic diseases, a follow-up study was started to investigate all patients who for the first time visited the outpatient clinic of the Department of Rheumatology in the period from 1983 to 1986 and who had detectable ANA. Patients with anti-dsDNA antibodies were excluded from evaluation. In total 65 patients could be included in the study, with a mean duration of follow-up of 9.3 years (range 2-16 years). During follow-up a specific rheumatic diagnosis could be established in 38 patients, on 75% of the patients within 2 years of follow-up, and in 90% within 5 years. Five patients developed a non-rheumatic disease. For the remaining 22 patients, diagnosis was not conclusive. These patients without a conclusive diagnosis had a mild clinical picture, which remained stable during follow-up. In conclusion 58% of patients presented with rheumatic symptoms and detectable ANA developed an overt rheumatic disease, usually within the first 5 years of follow-up.
Antibodies, Antinuclear↗
Systemic lupus erythematosus: clinical features in patients with a disease duration of over 10 years, first evaluation.
OBJECTIVE: Most information available about the disease course of patients with systemic lupus erythematosus (SLE) is restricted to the first 5 yr after disease onset. Data about the disease course 10 yr after disease onset are rare. The aim of this multicentre study was to describe the outcome of SLE patients with a disease duration of >10 yr. METHODS: Outcome parameters were the SLE Disease Activity Index (SLEDAI), the European Consensus Lupus Activity Measure (ECLAM), the Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index (SLICC/ACR), a global damage index (DI) and required treatment. In 10 different European rheumatology centres, all SLE patients who were evaluated in the last 3 months of 1994, and who had been diagnosed with SLE at least 10 yr ago, were included in the study. RESULTS: It should be stressed that our results are confined to a patient cohort, defined by a disease duration of at least 10 yr, and who are still under clinical care at the different centres in Europe. These SLE patients still showed some disease activity, related to symptoms of the skin and musculoskeletal systems, next to the presence of renal involvement. A total of 72% of the patients needed treatment with prednisolone (</=7.5 mg). The cumulative damage was overall related to clinical features of the central nervous system (14%) and renal involvement (14%), next to deforming arthritis (14%), osteoporosis (15%) and hypertension (40%). The prevalences of obesity, Cushing appearance and diabetes are highly suggestive that the ongoing treatment and that in the past might have had an impact on the total sum of end-organ damage. CONCLUSIONS: After 10 yr, a high proportion of patients in our cohort continued to show evidence of active disease, defined by the SLEDAI as well as ECLAM. The DI was related to the involvement of the central nervous system, renal involvement and the presence of hypertension.
Adult↗
Extracellular granzymes A and B in humans: detection of native species during CTL responses in vitro and in vivo.
Activated CTLs and NK cells induce apoptosis via multiple mechanisms, including that termed granule exocytosis. The latter pathway consists of vectorial secretion of perforin and a family of granule-associated serine proteases (granzymes) to the target cell. To establish whether granzymes are released extracellularly during cytolytic reactions in vivo, ELISAs that measure the native enzymes were developed and were found to specifically detect granzyme A (GrA) and granzyme B (GrB) at picogram concentrations. Low levels of GrA and GrB were present in plasma of healthy individuals (GrA, 33.5 pg/ml (median); GrB, 11.5 pg/ml (median)), whereas significantly higher levels were present in patients with ongoing CTL response, i.e., patients suffering from infections by EBV or HIV type 1. Markedly elevated levels were also noted in synovial fluid of patients with active rheumatoid arthritis. The measurement of soluble granzymes should be useful to assess clinical disorders associated with activated CTL and NK cells. Furthermore, these results suggest that granzymes mediate biologic effects beyond their described role in apoptotic cell death.
Animals↗
[Clinical thinking and decision making in clinical practice. A patient with systemic lupus erythematosus and behavioral changes].
A 48-year-old man with systemic lupus erythematosus (SLE) was admitted with fever, headache and mental change. On admission he was treated with daily doses of cyclophosphamide 100 mg and prednisone 7.5 mg. Orientation and attention were diminished and visual examination revealed right-sided homonymous hemianopia. MRI of the brain showed a ring-enhanced, space occupying lesion in the left occipital lobe. An infectious disease cause was considered, because disease activity parameters of SLE were all negative (anti-dsDNA and the complement profile). The anti-Toxoplasma titre was elevated in cerebrospinal fluid (57 IU/ml) and in serum (1140 IU/ml), both IgG. A tentative diagnosis of Toxoplasma encephalitis was made and a trial anti-toxoplasmosis treatment with pyrimethamine and sulfadiazine was administered. Two weeks later the patient was normal at neurological examination and his brain MRI had greatly improved. The anti-Toxoplasma titre had dropped significantly.
Diagnosis, Differential↗
The Fc gammaRIIIA-158F allele is a risk factor for systemic lupus erythematosus.
OBJECTIVE: To study whether the Fc gammaRIIIA-158V/F polymorphism, which affects IgG binding affinity, is a risk factor for systemic lupus erythematosus (SLE). METHODS: We genotyped a group of 70 Caucasian SLE patients for all known Fc gammaR polymorphisms. Of this group, 45 patients (64%) had nephritis. In 35 patients, this diagnosis was confirmed by renal biopsy. RESULTS: In the total group of 70 SLE patients, the frequency of the Fc gammaRIIIA-158F allele was 0.74, versus 0.57 in healthy controls (P = 0.003). The genotype distribution of the Fc gammaRIIIA-158V/F polymorphism was also significantly different from that of the control population (P = 0.004). The distribution of the other Fc gammaR polymorphisms--Fc gammaRIIA-131R/H, Fc gammaRIIIB-NA(1,2), and Fc gammaRIIIA-48L/R/H--was similar in SLE patients and controls. CONCLUSION: In our group of SLE patients, only the distribution of the alleles of the Fc gammaRIIIA-158V/F polymorphism was significantly different from that in the control group. This might indicate that macrophage expression of the Fc gammaRIIIA-158F isoform is involved in the disturbed clearance of immune complexes in patients with SLE.
Alleles↗