Antibodies to beta2-glycoprotein I: a potential marker for clinical features of antiphospholipid antibody syndrome in patients with systemic lupus erythematosus

OBJECTIVE: To clarify risk factors for the development of clinical features of antiphospholipid syndrome (APS) in patients with anticardiolipin antibodies (aCL) in systemic lupus erythematosus (SLE). METHODS: We studied 65 SLE patients, all with positive IgG and/or IgM aCL. Patients were divided into 2 groups; I: 29 SLE patients with features of APS (SLE/APS) and II: 36 aCL positive SLE patients without any feature of APS (SLE/aCL). Serum samples were collected from our serum bank. Anti-beta2-glycoprotein I (anti-beta2-GPI) were tested by ELISA using irradiated plates in the absence of cardiolipin. Anti-dsDNA antibodies were tested by standard Farr assay. RESULTS: There were no major differences between SLE clinical manifestations in both groups. However, the frequency of IgG anti-beta2-GPI was markedly increased in SLE/APS (18/29, 62%) than in SLE/aCL (4/36, 11%) (chi-squared 18.6, p=0.0001). The levels of anti-dsDNA antibodies in the same samples were slightly lower in SLE/APS. CONCLUSION: Our data suggest that increased levels of IgG anti-beta2-GPI may be a specific feature of SLE/APS patients rather than reflecting a polyclonal B cell activation.     

Elevated anticardiolipin antibodies in autoimmune haemolytic anaemia irrespective of underlying systemic lupus erythematosus

In patients with systemic lupus erythematosus (SLE) and concomitant Coombs positive autoimmune haemolytic anaemia (AIHA) anticardiolipin antibodies (aCL) are found more frequently and at higher titres than in SLE patients without AIHA. In order to assess if aCL elevation is primarily associated with the underlying SLE, or with AIHA itself, we examined AIHA patients with and without underlying SLE for the presence of aCL. aCL (IgG and IgM) were determined by ELISA in 74 SLE patients without AIHA, 22 SLE patients with AIHA, 50 patients with idiopathic AIHA (warm-reactive autoantibodies), 52 patients with idiopathic AIHA (cold-reactive autoantibodies) and 50 healthy controls. The mean IgG and IgM aCL titres in SLE patients without AIHA (IgG 37.0 U/ml, IgM 8.9 U/ml) were significantly elevated compared with the values in healthy controls (IgG 9.1 U/ml, IgM 3.2 U/ml; P < 0.005). The mean aCL levels in SLE patients with AIHA (IgG 53.2 U/ml, IgM 28.2 U/ml) were higher than in SLE patients without AIHA (P = 0.09 for IgG, P < 0.005 for IgM). Interestingly, the mean aCL levels of patients with idiopathic AIHA (warm-reactive autoantibody type: IgG 29.2 U/ml, IgM 19.3 U/ml; cold-reactive autoantibody type: IgG 27.4 U/ml, IgM 18.9 U/ml) were also significantly elevated compared with healthy controls P < 0.001). As aCL are elevated not only in SLE (with and without concomitant AIHA) but also in idiopathic AIHA it can be speculated that aCL are involved in the pathomechanism of autoantibody-induced erythrocyte destruction per se irrespective of an underlying SLE.     

Antibodies to beta 2-glycoprotein I and clinical manifestations in patients with systemic lupus erythematosus

OBJECTIVE: To investigate whether anticardiolipin antibodies (aCL) in patients with systemic lupus erythematosus (SLE) bind to beta 2-glycoprotein I (beta 2GPI), and to search for a relationship between the presence of IgG and/or IgM anti-beta 2GPI antibody and clinical manifestations in SLE patients. METHODS: IgG and IgM anti-beta 2GPI in 308 Japanese SLE patients were measured using phospholipid-independent enzyme immunoassays. Relationships to clinical histories and to various laboratory data were examined. RESULTS: The values of anti-beta 2GPI and aCL, as measured by conventional enzyme immunoassay, showed a strong correlation, but the anti-beta 2GPI assay was more useful in distinguishing beta 2GPI-dependent aCL from beta 2GPI-independent aCL. The presence of IgG anti-beta 2GPI was associated with an increased frequency of a history of thrombosis. Comparisons of various laboratory data suggested that the titer of anti-beta 2GPI may fluctuate with disease activity. CONCLUSION: The results suggest that pathogenic aCL is directed against structurally altered beta 2GPI and that enzyme immunoassay for anti-beta 2GPI may prove useful in evaluating the risk of thrombosis and monitoring the clinical course in patients with SLE.     

Prevalence of antiphospholipid antibodies in patients with ankylosing spondylitis

OBJECTIVE: To establish the prevalence of antiphospholipid antibodies (aPL) in a group of patients with ankylosing spondylitis (AS). The relation of the antibodies with different clinical and analytical features was studied. METHODS: Eighty-four patients with AS (71 men) and 40 age and sex matched controls were studied. aPL determinations included: anticardiolipin antibodies (aCL) of the IgM, IgG, and IgA classes, the presence of lupus anticoagulant (LAC), and a false positive serologic test for syphilis. Comparisons between variables were done by Student t test, Mann-Whitney test and Chi squared test. Correlations between aPL and clinical variables were performed by Pearson coefficients. RESULTS: Twenty-four patients with AS (29%) has positive IgG aCL, compared with only 2 cases in the control group (5%) (p < 0.002). There were no differences in other aPL determinations between patients and controls. There was no correlation between the presence of aCL (IgG, IgM, or IgA) and LAC and the different aspects of the disease. Two patients fulfilled the criteria for antiphospholipid syndrome. CONCLUSION: Our results indicate the presence of IgG aCL in patients with AS higher than in the normal population but their relation with thrombosis and other systemic manifestations seems weak.     

Anticardiolipin antibodies in systemic lupus erythematosus: clinical correlates, HLA associations, and impact on survival

OBJECTIVE: To determine the frequency and clinical and HLA associations of anticardiolipin (aCL) antibodies in patients with systemic lupus erythematosus (SLE), as well as their impact on survival. METHODS: We studied 139 patients with SLE seen at a university based practice. We tested for clinical, laboratory, and HLA associations with levels of aCL antibody isotypes either in sera available in the bank (distant past) or in 2 samples. Demographic, clinical, laboratory, and HLA data were subjected to univariate survival analysis; variables of importance were entered into Cox multivariate regression analyses. RESULTS: aCL antibodies (any isotype) were present in 57 (41.0%) of the 139 patients tested in the distant past sample, and in 23 (32.3%) as a persistent event in the 71 patient subgroup tested twice. IgG aCL were significantly associated with deep venous thrombosis (DVT) (p = 0.04). No other clinical or HLA association was found with aCL positivity. In the survival analyses, older age at diagnosis, presence of major infections, endstage renal disease, and IgM aCL antibody positivity in the distant past emerged as important independent factors adversely affecting survival. In the subgroup tested twice for aCL antibodies (n = 71), persistent IgM aCL antibody positivity (n = 10) emerged as an important independent factor. Among the subgroup of patients that had HLA data available (n = 88), HLA-DQw7 and thromboembolic events also adversely affected survival. CONCLUSION: We confirmed the association of IgG aCL antibody positivity with DVT, and the impact on survival of endstage renal disease, major infections, and older age at diagnosis. IgM aCL antibody positivity present either as an isolated event in the distant past or as a persistent finding, thromboembolic events, and HLA-DQw7 emerged as important prognostic factors.     

Platelet lactate dehydrogenase activity in systemic lupus erythematosus: correlation with anticardiolipin antibodies

OBJECTIVE: To evaluate lactate dehydrogenase (LDH) activity in platelet subpopulations in systemic lupus erythematosus (SLE) and to correlate platelet LDH activity with concentrations of anticardiolipin antibody (aCL). METHODS: Twelve female patients with SLE and 12 age matched female control subjects were studied. Platelets were separated on the Percoll gradient, their density values controlled by density marker beads. LDH activity was measured after platelet lysis, expressed as nU/fl. ELISA were used to measure levels of IgG and IgM aCL. RESULTS: A significant increase of LDH activity with a significant correlation to IgG and IgM aCL were found in small, light platelets with a volume < 5 mu 3 compared to large, dense platelets and to controls. LDH activity did not correlate with immunoglobulin classes, anti-DNA antibodies, and complement fractions in small and large SLE platelets. CONCLUSION: Our data suggest a possible chronic activation of subpopulations of small platelets in patients with SLE independent of thrombotic process. Low levels of aCL can mediate small platelet activation. Quantitative and qualitative analysis of the small, light platelets can serve a clinical diagnostic purpose as an in vivo platelet activation index in SLE.     

Association between antiphospholipid antibodies and arterial or venous thrombosis/thrombocytopenia

The relationship between thrombotic or thrombocytopenic complications and the existence of anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LA) was studied in 146 patients with systemic lupus erythematosus (SLE). The prevalence of arterial thrombosis was obviously higher in patients who had both aCL and LA than in patients with either aCL or LA alone or in those with neither. Since a substantial fraction of the former group of patients with arterial thrombosis also had thrombocytopenia, there is a possibility that aCL and LA might enhance platelet activation and aggregation. To test this hypothesis, we studied the in vitro effects of aCL and LA on the enhancement of platelet activation by flow cytometric analysis using anti-CD62P and anti-CD41 monoclonal antibodies directed against platelet activation-dependent granule-external membrane (PADGEM) protein and platelet glycoprotein IIb (GPIIb). The IgG fraction purified from aCL+.LA+ plasma apparently enhanced platelet activation induced by adenosine diphosphate (ADP) at a low concentration, but IgG fractions from aCL+.LA- or aCL-.LA+ plasma did not cause enhancement of platelet activation. These results suggest that aCL and LA may cooperate to promote platelet activation, and may be involved, at least partially, in the pathogenesis of arterial thrombosis in patients with SLE.     

Detection of isotype-specific autoantibodies to calpastatin in sera from patients with rheumatic diseases using heat-treated HeLa cell extract as an antigen source for immunoblotting

To detect immunoglobulin isotype-specific autoantibodies to native human calpastatin in patients with rheumatic diseases, we performed immunoblot analysis using the heated HeLa cell extracts to enrich heat-resistant calpastatin. The calpastatin molecule that was apparently migrated to 110 kD by SDS-PAGE was confirmed to react with monoclonal anti-human calpastatin antibody in immunoblotting. IgG antibodies to calpastatin were detected in 22 of 48 sera (46%) from patients with RA, whereas only 20% (5/25), 11% (2/19) and 13% (2/15) of sera from SLE, SSc and PM/DM had IgG anti-calpastatin antibodies, respectively. IgM antibodies were also found in 40% (19/48) of RA and 12% (3/25) of SLE patients but not detected in sera from patients with other rheumatic diseases. IgA antibodies were found in only one RA and one SLE serum. In RA, 7 of 48 sera (15%) had IgM antibodies alone, but all SLE sera with IgM antibodies had IgG antibodies. Thus, anti-calpastatin autoantibodies were detected by using the native human calpastatin. Although these autoantibodies were found in patients with various rheumatic diseases, they were present in RA patients at the highest frequency. In particular, the presence of IgM antibodies appeared to be more specific in RA patients.     

Evidence of autoantibodies to cell membrane associated DNA (cultured lymphocytes): a new specific marker for rapid identification of systemic lupus erythematosus

OBJECTIVE: Autoantibodies to cell membrane associated DNA are described in systemic lupus erythematosus (SLE). The specificity of these antibodies differ from antibodies to nuclear DNA. METHODS: Using indirect immunofluorescence, a specific IgG was detected giving a characteristic pattern of continuous peripheral membrane fluorescence on cultured B-lymphocytes. RESULTS: This pattern was observed in 53 of 80 serum samples of SLE patients but absent in the serum samples of the control populations: 15 rheumatoid arthritis, 38 ankylosing spondylarthritis, 17 non-inflammatory osteopenic patients, and 224 blood donors. In 34 Sj?gren syndrome's patients one only showed a positive test. The cmDNA specificity of these antibodies was confirmed by pattern extinction with DNAse but not RNase or protease pre-treatment of the cells. IgG to cmDNA, separated by absorption/elution from purified cmDNA immobilised on DEAE-nitrocellulose reproduced the immunofluorescence pattern pictures. Extensive serum depletion of anti-double strand or single strand DNA antibodies by absorption to cellulose bound ds- or ss-DNA affected marginally the pericellular fluorescence revealing some minor cross reactivity with nuclear DNA. Moreover, in SLE patients without detectable antibody to ds-DNA, pericellular fluorescence could be visible. CONCLUSION: This novel rapid immunofluorescence method may serve as an identification test of SLE patients. Given its positive (97.1%) and negative (92.9%) predictive value, sensitivity (66%) and specificity (99.5%), it improves on other diagnostic tests such as the detection of antibodies to Sm.     

Arterial disease in lupus and secondary antiphospholipid syndrome: association with anti-beta2-glycoprotein I antibodies but not with antibodies against oxidized low-density lipoprotein

The prevalence and clinical significance of antibodies against beta2-glycoprotein I (anti-beta2GPI) and antibodies against oxidized low-density lipoprotein (anti-ox-LDL) were evaluated as potential indicators of arterial disease in patients with systemic lupus erythematosus (SLE) and SLE with secondary antiphospholipid syndrome (APS). IgG anti-beta2GPI and IgG anti-ox-LDL were measured by enzyme-linked immunosorbent assay (ELISA) in serum samples from 118 patients with SLE, including 40 with secondary APS. IgG anti-beta2GPI were positive in 17% (20/118) of SLE patients. The presence and titres of IgG anti-beta2GPI were strongly associated with a history of arterial thrombosis. Haemolytic anaemia was also significantly associated with the presence of IgG anti-beta2GPI. The prevalence of IgG anti-ox-LDL was 53% (63/118), but there was no association with arterial thrombosis. No correlation between the values of anti-ox-LDL and those of anti-beta2GPI was found. These results suggest that IgG anti-beta2GPI could be a marker for arterial thrombosis in SLE patients, while IgG anti-ox-LDL were not associated with arterial disease in this group of lupus patients.     

Anti-DNA, anti-deoxyribonucleoprotein and rheumatoid factor measured by ELISA in patients with systemic lupus erythematosus, Sj?gren's syndrome and rheumatoid arthritis

Serum concentrations of anti-DNA and anti-deoxyribonucleoprotein (NP) antibodies were measured in parallel by standardized ELISA methods with a polyvalent anti-immunoglobulin conjugate in patients with systemic lupus erythematosus (SLE), Sj?gren's syndrome (SS) and rheumatoid arthritis (RA). High levels of these antibodies predominated in systemic lupus erythematosus. While an appreciable incidence of antibodies also occurred in SS and RA, they were mostly at lower levels. By using heavy chain-specific anti-immunoglobulin conjugates, IgG antibodies to both DNA and NP were found in SLE more frequently and at higher levels than were IgM antibodies. In contrast, IgM antibodies to DNA and NP predominated in SS and RA. The immunoglobulin class of the anti-DNA and anti-NP responses in a given SLE patient were not infrequently different. For example, a patient might show a very high IgG but low IgM anti-DNA value, with the reverse being true for anti-NP. IgG anti-DNA antibodies were significantly associated with depressions of C3. During changes in SLE serology, normalization of DNA binding by Farr radioimmunoassay and/or complement was most frequently associated with normalization of the IgG anti-DNA antibody concentrations. In patients simultaneously possessing elevated levels of anti-DNA, anti-NP and rheumatoid factor (RF), absorption with aggregated human IgG usually decreased only the RF activity. In some, however, such absorption decreased all three antibody values simultaneously. The latter findings support observations that some RF possess antinuclear properties.     

Bilateral diffuse hypoperfusion of posterior temporoparietals and occipitals in Tc-99m HMPAO brain SPECT in a patient with noncommunicating hydrocephalus

We measured class-specific antibodies to the mycobacterial hsp70 protein in 67 patients with diabetes mellitus (27 type 1 and 40 type 2) with or without vascular complications. Using ELISA, the levels of IgG and IgM antibodies in the sera of diabetic patients did not significantly differ either from those of healthy control subjects or between both types of diabetes, regardless of gender, disease duration, HbA1 level, or type of vascular complication. In patients with type 2 diabetes, the mean serum IgA levels were significantly higher than those in their matched controls [274(71) mg/dl vs 208(88) mg/dl; P < 0.01]. In this group of patients, the IgA antibody titer was significantly correlated to the serum IgA level (r = 0.334; P < 0.01). Serological autoimmunity (IgG or IgM type) to hsp70 protein is common in both the normal and the diabetic population. The increased IgA levels and anti-hsp70 IgA titers in the sera of diabetics suggest a possible role of IgA in the pathogenesis of the vascular complications of diabetes mellitus.     

Urinary loss of immunoglobulin G anti-F(ab)2 and anti-DNA antibody in systemic lupus erythematosus nephritis

The objective of this study was to determine whether the low levels of serum immunoglobulin G (IgG) anti-F(ab)2 seen in some patients with active systemic lupus erythematosus (SLE) were directly related to the deposition of antibody with this specificity in the kidney or alternatively to the urinary loss of IgG anti-F(ab)2. Serum Levels of IgG anti-F(ab)2, anti-tetanus toxoid, and anti-ds DNA antibody were measured in parallel with urinary excretion of these same 3 antibodies in 28 patients with SLE nephritis and in 28 control patients with other forms of chronic kidney disease. Low levels of both serum IgG anti-F(ab)2 or anti-tetanus antibody appeared to correlate with increased levels of urinary loss of these same antibodies in some patients with SLE and in control subjects with kidney disease. However, urinary loss could not account for low serum levels of either IgG antibody in many subjects. Quantitative 24-hour urinary losses of IgG anti-F(ab)2 and anti-DNA were much higher in patients with SLE than in control subjects with kidney disease (P < .05), whereas amounts of IgG urinary loss of anti-tetanus were similar in patients with SLE and in control subjects. In nearly 1 third of SLE nephritis patients, 13% to 53% of total excreted urinary IgG showed anti-DNA enzyme-linked-immunosorbent assay reactivity. Urinary IgG in many patients with SLE showed both anti-DNA and anti-F(ab)2 reactivity, but dual anti-DNA/F(ab)2 specificity was more pronounced in affinity-isolated serum IgG anti-DNA or anti-F(ab)2 than in excreted urinary IgG molecules. The affinity of urinary IgG for either DNA or F(ab)2 was much lower than the same antibody activities measured either in serum or in kidney biopsy eluates. When the relative affinity of anti-DNA antibody in serum, urine, and kidney biopsy eluate was measured in parallel, the highest affinity antibody was found in kidney biopsy eluates, followed by serum antibody with urine antibody affinity showing the lowest values. These findings suggest a relative concentration of the highest affinity, doubly reactive IgG anti-DNA/F(ab)2 in SLE kidney tissues during SLE nephritis and implicate this process as an important factor in ongoing tissue damage.     

Salivary immunoglobulin concentrations in patients with epilepsy treated with carbamazepine

Various anti-epileptic drugs may affect the immune system. An IgA-depressing effect of carbamazepine has been proposed, but only serum concentrations have been studied. IgA constitutes a small fraction of the serum immunoglobulins, while it is the predominating one in external secretions. In the present study the concentrations of IgA, IgG and IgM in unstimulated saliva were determined by single radial immunodiffusion in 34 patients with partial epilepsy, and being treated with carbamazepine alone. Median salivary IgA concentration in the patients was 208 x 10(-3) g/l, compared to 150 x 10(3) g/l in 41 healthy controls. Salivary IgG and IgM concentrations were also somewhat higher in the patients than in the controls, while the albumin concentrations were similar in the two groups. However, the differences in the immunoglobulin concentrations between patients and controls were not significant at a 5% level. There was no significant correlation between the concentrations of IgA in saliva and serum.     

Anticardiolipin antibodies are associated with pulmonary hypertension in patients with mixed connective tissue disease or systemic lupus erythematosus

Anticardiolipin antibodies (aCL) were studied in relation to pulmonary hypertension (PH) in 22 patients with mixed connective tissue disease (MCTD) or systemic lupus erythematosus (SLE). The mean pulmonary arterial pressure (mPAP) values were similar in the 12 MCTD and 10 SLE patients: 26 +/- 11 and 25 +/- 11 mm Hg, respectively. However, the frequency of PH was higher in SLE (60%) than in MCTD patients (33%). The titers of aCL were significantly higher in SLE (38 +/- 27 IU/ml) than in MCTD (17 +/- 7 IU/ml; p < 0.02). Two SLE patients with high titers of aCL had multiple cerebral infarction and transverse myelitis, and deep vein thrombosis, respectively. A significant correlation between the titers of aCL and mPAP was observed in patients with MCTD (p < 0.05), but not in patients with SLE.     

Anticonvulsant and glutamate release-inhibiting properties of the highly potent metabotropic glutamate receptor agonist (2S,2''R, 3''R)-2-(2'',3''-dicarboxycyclopropyl)glycine (DCG-IV)

IgA has an important function in the gastrointestinal immune system. We investigated IgA anti-ganglioside antibodies in Guillain-Barré syndrome (GBS) and Fisher's syndrome (FS) subsequent to Campylobacter jejuni enteritis. In previous studies, serological diagnosis of C. jejuni infection was based on the detection of IgG, IgA, and IgM anti-C. jejuni antibodies. Our study, however, showed that the detection of IgG anti-C. jejuni antibody alone was sufficient for the serological diagnosis of antecedent C. jejuni enteritis in GBS and FS, when the cut-off level was defined for results of sera from C. jejuni-isolated patients. Serological evidence of C. jejuni infection was found in 62 (31%) of 201 GBS patients and 12 (18%) of 65 FS patients. IgA anti-GMI antibody was detected in sera from 33 (16%) of the GBS patients, 1 (2%) of the FS patients, and none of the 46 normal control subjects. IgA anti-GM1 antibody titers were significantly higher in the GBS patients with positive C. jejuni serology than in those with negative serology (P < 0.0001) or the FS patients with positive C. jejuni serology (P = 0.007). IgA anti-GQ1b antibody was detected in sera from 18 (28%) of the FS patients, 9 (4%) of the GBS patients, and none of the normal control subjects. FS patients with positive C. jejuni serology had significantly higher titers of IgA anti-GQ1b antibody than those with negative serology (P = 0.01) or the GBS patients with positive C. jejuni serology (P < 0.0001). We conclude that anti-GM1 and anti-GQ1b IgA antibodies are closely associated with antecedent C. jejuni enteritis in GBS and FS, respectively.     

Overexpression of c-myc induces apoptosis at the prophase of meiosis of rat primary spermatocytes

Serum samples from 36 cervical carcinoma patients, 33 patients with high-grade squamous intraepithelial lesions, and 31 cytologically normal women were tested by enzyme-linked immunosorbent assay (ELISA) using human papilloma virus type 6 (HPV 6) and HPV 16 virus-like particles as antigens. Forty serum specimens from 1-year-old children were used to assign cutoff points. When serum samples from the subjects infected with HPV 16 were tested in an HPV 16 ELISA detecting immunoglobulin A (IgA), IgG, and IgM binding, 61% showed IgA, 44% showed IgG, and 39% showed IgM reactivity. Of HPV 6- or 11- or HPV 18-infected subjects. fewer than 17% showed IgA or IgG responses and 33% showed IgM reactivity. In contrast, 13% showed IgA, 10% showed IgG, and 16% showed IgM reactivity in the HPV DNA-negative controls. The results suggest that the IgA and IgG responses are HPV 16 specific and the IgM response is cross-reactive to different HPV types. On the other hand, the serological responses to HPV 6 did not differ in the patient and control groups. The percentages of patients positive for both IgA and IgG antibodies were significantly higher in the groups with high-grade squamous intraepithelial lesions (12% [4 of 33]; P = 0.04) and cancer (17% [6 of 36]; P = 0.02) than in the healty women (0% [0 of 31]), and the percentages for either IgA or IgG were higher for the cancer group (47% [17 of 36]; P = 0.01) than in the normal group (19% [6 of 31]). Most sera positive for IgA and IgG in the patient groups showed higher titers than those in the normal group. All these results suggest that high IgA and IgG responses are good indicators for estimating HPV 16 infection.     

Antiphospholipid antibodies: an epiphenomenon in Tourette syndrome

Antiphospholipids (aPLAs) have been previously identified in children with Tourette syndrome (TS), which has led to the speculation that these antibodies might have a pathophysiologic role in this disorder. Therefore, 21 healthy children and adolescents with TS, whose ages ranged from 7 to 17 years, underwent laboratory studies designed to diagnose the lupus anticoagulant, anticardiolipin (aCL) antibodies [immunoglobulin (Ig) G, IgA, and IgM], and antinuclear antibodies. Although five subjects had at least one value that differed from accepted laboratory standards, the changes were marginal in four of them. Lupus anticoagulant was identified in one patient, based on a minimal requirement of a prolonged dilute Russell viper venom time, clotting studies that did not correct after mixture with normal plasma, and an abnormal platelet neutralization procedure. A prolonged (but correctable) activated partial thromboplastin time was found in one individual, and aCL IgG was marginally increased in three subjects. Two (10%) of a control population of 20 same-age children also had low positive aCL IgG levels. There were no differences in tics (onset, type, frequency, severity, and family history) or comorbid features between children with normal or "abnormal" laboratory study results. Our data suggest that the presence of aPLAs in TS represents an epiphenomenon rather than a pathophysiologic mechanism.     

Differential roles of the anti-ribosomal P antibody and antineuronal antibody in the pathogenesis of central nervous system involvement in systemic lupus erythematosus

OBJECTIVE: To compare the role of antibodies against the ribosomal P protein (anti-P) with that of antibodies against neuronal cells (anti-N) in the pathogenesis of central nervous system (CNS) involvement in systemic lupus erythematosus (SLE). METHODS: Sera from 87 SLE patients (27 with non-CNS SLE, 34 with lupus psychosis, and 26 with nonpsychotic CNS lupus) and from 20 control patients with neurologic manifestations without SLE and cerebrospinal fluid (CSF) from 41 patients with CNS lupus and from the 20 control patients were assayed for IgG anti-P and anti-N by an enzyme-linked immunosorbent assay (ELISA) using ribosomal P synthetic peptides and by a cell ELISA using paraformaldehyde-fixed SK-N-MC neuroblastoma cell lines, respectively. RESULTS: Serum anti-P levels were significantly elevated in patients with lupus psychosis compared with those with non-CNS SLE or those with nonpsychotic CNS lupus, whereas there were no significant differences in serum anti-N levels among these 3 groups. In contrast, CSF anti-N levels were significantly elevated in patients with lupus psychosis compared with those with nonpsychotic CNS lupus and compared with non-SLE controls, whereas CSF anti-P were not detected in most of the patients. CONCLUSION: The results indicate that anti-P in the systemic circulation and anti-N in the CSF are involved in the development of lupus psychosis.