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Background: Anaphylactic reactions during anesthesia are mainly the result of muscle-relaxant (MR) drugs. Skin tests, serologic detection of specific IgE, and in vitro leukocyte histamine release are used to investigate MR allergy. Objective: We describe a new assay that is based on the detection by flow cytometry of the altered expression of plasma membrane molecules of MR-activated basophils. Methods: For this assay, which we have named the BASIC assay, basophils are incubated in vitro with MR, after which they are fixed and then triple labeled with fluorescein-conjugated anti-CD63, tandem dye R-phycoerythrin-cyanin 5.1 conjugated anti-CD45, and R-phycoerythrin conjugated anti-IgE. The resulting B asophils' A ltered S urface I mmunofluorescence is detected by flow C ytometry (BASIC). Results: Forty-one patients who had an allergic reaction during general anesthesia and 23 control subjects without such a history were studied. All included subjects' basophils were tested in the BASIC assay with at least 4 MR: suxamethonium, gallamine, vecuronium, and pancuronium. After reaction of the basophils of the MR-allergic patients with MRs, increased surface expression of CD63 and CD45 and decreased expression of IgE were detected. Increased expression of CD63 was observed most frequently and it was stronger than the alteration of the 2 other markers. Cross-reactivity between MRs commonly occurred. MRs diluted 10 –1 activate the basophils of the control subjects, suggesting that at relatively high concentrations MRs are also nonspecific basophil activators. Conclusion: In the diagnosis of MR allergy, the BASIC assay has a good specificity but a low sensitivity, and it correlates strongly with skin test results. It is currently appraised for the diagnosis of anaphylactic reaction induced by other classes of drugs. (J Allergy Clin Immunol 1999;104:411-8.)

Immunodeficiency related to HIV may increase the incidence of EBV-associated lymphomas, by altering EBV-specific immune control and consequently favoring EBV reactivation. The aim of the present study was to assess the relationship between the decrease of EBV-specific cellular immunity and the increase of EBV reactivation in a prospective cohort of 72 unselected HIV-infected individuals. EBV-specific immunity was evaluated by a highly sensitive IFN-gamma ELISPOT assay using 22 peptides mimicking latent and lytic antigens, and circulating mononuclear (PBMC) EBV DNA load was quantified by real-time quantitative PCR. The mean circulating cell-associated EBV DNA load was higher in HIV-infected patients (639 copies/10(6) PBMC) than in healthy controls (21, n = 14) ( P = 0.005) and was higher in patients with CD4(+) T-cell count below 350/microL than that in patients harboring higher CD4(+) T-cell count (1112 vs. 389, P = 0.003). The mean intensity of EBV-specific cellular responses was lower in HIV-infected patients than in controls ( P = 0.001), even in patients with CD4(+) T-cell count above 350/-microL ( P = 0.007). The number of EBV peptides recognized was lower in HIV-infected patients than in controls (frequency: 0.44 vs. 0.67; P = 0.02), indicating reduced polyclonality in HIV-infected patients. The polyclonality was 1.5-fold lower in HIV-infected patients with CD4(+) T-cell count below 350/-microL ( P =0.007). For EBV load >1000 copies/10(6) PBMC, the levels of cell-associated EBV DNA and those of EBV-specific cellular immunity, either in intensity or in polyclonality, or both, were inversely correlated. These findings demonstrate early impairment of the EBV-specific cellular immune control with progressive increase of EBV reactivation in the course of HIV infection. These observations likely provide a basis for appreciating the risk to develop non-Hodgkin's lymphomas in HIV-infected individuals.

Background: The prevalence of antibodies to cardiolipin (a-CL) in patients with Raynaud's phenomenon (RP) and/or related disorders (rD) is not known. Objective: The purpose of this study was to determine the prevalence of these antibodies. Methods: We assayed IgG a-CL in 230 consecutive patients with RP/rD and compared the results with those in a series of 230 control blood donors. Results: Sixteen percent of patients were a-CL positive versus 7.8% of the control donors ( p = 0.014). The prevalence of a-CL positivity was 8.7% for primary RP, 10.5% for secondary RP, 8% for chilblains, 25% for essential acrocyanosis, 20% for connective tissue diseases, and 17% for undifferentiated connective tissue diseases. Among patients with digital necrosis, 24% were a-CL positive. Conclusion: The prevalence of abnormal a-CL titers is higher in patients with RP/rD than in control donors, especially in patients with a connective tissue disease. (J Am Acad Dermatol 1998;38:555-8.)

The silicone implant controversy wavers between reassuring epidemiological studies and about 300 case reports of patients developing a definite or incomplete/atypical connective tissue disease (CTD) after receiving a silicone gel-filled breast implant (SBI). Since Hashimoto's thyroiditis (HT) is rarely reported in this context, we report here two new cases of HT associated with a history of bilateral cosmetic SBIs. The first patient was a 45-year-old white woman who had SBIs in 1976. In 1991 she developed HT, evolving to thyroid deficiency which was compensated with levothyroxine treatment. In addition, the patient complained of fatigue, arthralgia, morning stiffness and developed a sicca syndrome necessitating artificial tears. The 1995 evaluation disclosed the presence of antinuclear antibodies at a titre of 1/640, and high level anti-thyroid microsomal antibodies (1/256,000). Gamma globulins rose to 22.6%. Thyroid ultrasonography showed an enlarged thyroid gland with a diffusely hypoechogenic pattern. The implants were painful, and in 1996 they were removed. Microscope examination of the fibrous capsule surrounding the prostheses showed extremely dense connective tissue with fibrosis. The second patient was a 55-year-old white woman who had SBIs in 1984. In 1995, she developed HT with clinical pain and tenderness of the thyroid gland, with mild hyperthyroidism and positive antithyroglobulin antibodies, and was given corticosteroid treatment for 5 months. In 1996, the implants were again painful and the patient developed positive antinuclear antibodies with a titre of 1/200. Ultrasonography showed a heterogeneous thyroid gland, and implant removal was advised. Hashimoto's thyroiditis is recognized as a subset of chronic auto-immune thyroiditis, and its association with SBI is rare. In these 2 observations, an association without relation is possible, but a future survey of similar cases seems warranted.

In order to investigate the clinical value of anti-mitochondrial antibodies type 5 (anti-M5), we carried out a retrospective study on 48 patients with these antibodies. Seventeen of these 48 patients (35%) satisfied at least 4 criteria of the revised American Rheumatism Association classification of SLE. Twenty-nine (61%) had at least one clinical manifestation of anti-phospholipid syndrome; thirteen had symptoms consistent with primary anti-phospholipid syndrome; five had isolated recurrent thrombosis; five had Evans' syndrome; four had auto-immune haemolytic anaemia; two had immunologic thrombocytopenia. Two of the 48 patients had no clinical manifestations, but only anti-M5 and a false laboratory test for syphilis (FBTS). Our data confirm that patients with anti-M5 have a high prevalence of: 1) thrombosis (42% had three or more deep thromboses) and fetal loss (21%); 2) auto-immune cytopenia with idiopathic thrombocytopenic purpura (29%) and auto-immune haemolytic anaemia (54%); 3) laboratory markers of anti-phospholipid syndrome (lupus anticoagulant (71%), FBTS (95%) and anticardiolipin antibodies (aCL) (71%). For 32 patients with anti-M5, anti-beta 2 glycoprotein I antibodies were also tested; 12 (38%) were positive, all of whom had IgG aCL, ie none had anti-beta 2GPI antibodies without aCL. There was no association between the presence of anti-beta 2GPI antibodies and recurrent thrombosis among patients with anti-M5. All these findings suggest that anti-M5 is another marker of the antiphospholipid syndrome. Even though the prevalence of anti-M5 is low, especially in SLE, it was the only marker of the anti-phospholipid syndrome in two patients; this appears to justify routine screening for these antibodies.

The aim of this study was to evaluate the prevalence and the clinical signification of non organ specific autoantibodies in chronic hepatitis C.We studied retrospectively 158 consecutive patients (97 with chronic hepatitis C, 24 with chronic hepatitis B, 67 with alcoholic cirrhosis) and 100 blood-donors.The prevalence of anti-nuclear and anti-smooth muscle antibodies was lower in blood donors than in patients (P0.001), but was comparable among the 3 groups of patients. The anti-liver-kidney microsome type 1 antibodies were detected only in patients with chronic hepatitis C (6%). The serum gammaglobulin level was significantly higher in patients with hepatitis C and anti-nuclear antibody titersor = 1/50. The anti-smooth muscle antibodies detected in patients with hepatitis C had no anti-actin specificity. The response to interferon was not related to the detection of non organ specific autoantibodies before treatment.Anti-nuclear or anti-smooth muscle antibodies are not characteristic of hepatitis C virus infection.

Recent studies have shown that hepatitis C virus antibodies are present in a large proportion of patients with autoimmune hepatitis type 2. We have studied 83 patients with liver/kidney microsome antibody-positive type 1 hepatitis. Hepatitis C virus antibodies were sought in every case by second-generation tests (hepatitis C virus enzyme-linked immunosorbent assay and recombinant immunoblot assay). Hepatitis C virus RNA sequences were sought in 22 patients (12 with recombinant immunoblot assay-positive results and 10 with recombinant immunoblot assay-negative results) by means of polymerase chain reaction and by use of primers located in the 5′ noncoding region. Sixty-four patients (77%) had positive results for hepatitis C virus antibodies in the enzyme-linked immunosorbent assay test, and 41 (49.3%) were confirmed by recombinant immunoblot assay. Hepatitis C virus RNA sequences were found in all the recombinant immunoblot assaypositive patients but in none of the 10 who were recombinant immunoblot assay-negative. The recombinant immunoblot assay-negative patients were younger than those who were positive (13 ± 11 vs. 50 ± 11 years) and had higher γ-globulin levels and liver/kidney microsome antibody-positive type 1 titers (61% had a titer of 1:1,000 or more, vs. only 17% of the recombinant immunoblot assay-positive patients). On the basis of these results, chronic hepatitis with liver/kidney microsome antibody-positive type 1 can be divided into two subgroups: (a) true autoimmune hepatitis type 2 (mainly observed in young women), with high titers of liver/kidney microsome antibody-positive type 1, and in which direct autoimmune mechanisms appear to be prominent; and (b) hepatitis C virus-associated hepatitis with liver/kidney microsome antibody-positive type 1 (generally affecting older patients, especially men), with low titers of liver/kidney microsome antibody-positive type 1, and in which the autoimmune process could be a consequence of hepatitis C virus infection. (HEPATOLOGY 1992;16:630–636.)

The authors report a case of Waldenstrom disease in which the IgM kappa immunoglobulin had an anti-smooth-muscle activity at a very high titre (1/100 000). This activity was found in the purified IgM but not in the Fab fragment; nevertheless, the immunofluorescence inhibition by this fragment is evidence in support of the anti-smooth-muscle activity of the IgM. The IgM specificity in this patient is different from the anti-smooth-muscle antibodies already described.

The synthesis of blocking antibodies has been demonstrated in ten patients undergoing rush immunotherapy (R-IT) with mite extracts: basophil degranulation performed on washed cells (Allergolam technique) did not differ significantly before and 10.8 (+/- 6.8) months after R-IT. Preincubation of allergen (100, 25, 10, and 5 micrograms/mL) with individual serum collected before R-IT did not decrease degranulation, but degranulation was significantly decreased when the allergen was incubated 30 minutes at 37 degrees C with individual serum collected after R-IT or with the IgG-fraction of a pool of sera collected in 22 treated patients. A linear correlation between the mean of degranulation and the log allergen concentration was observed in the two latter groups. The antigen neutralizing capacity of the IgG-fraction was studied on basophils of 11 "allergic donors." Antigen neutralizing capacity clearly increased with time of incubation with the allergen (15, 30, and 60 min), but was also significant without preincubation, eg, for 10 and 5 micrograms/mL allergen concentrations. These results indicate that the improvement of asthma usually noticed 2 months after R-IT is probably due, essentially, to blocking antibodies, since the sensitivity of the basophils is not modified significantly.

Six patients developed acute, subacute or chronic hepatitis after taking tielinic acid, a new diuretic used in the treatment of hypertension. Two died of acute liver failure. The condition was characterized by marked increase in serum transaminases, parenchymal necrosis and portal and/or lobular inflammatory fibrosis. In addition, the serum of all patients contained high titers of a liver/kidney microsomal antibody, which disappeared either after tienilic acid was discontinued or after prednisolone was introduced. The study shows that tienilic acid may be responsible for acute or chronic hepatitis and suggests that a liver/kidney microsomal antibody could be a sero-immunological marker of drug-induced liver disease.

Total eosinophil count (TEC) was done in 13 normal subjects, in 8 subjects before and 90 mn after a "French" breakfast and in 29 asthmatic patients. The geometric mean is higher (p less than 0,001) in asthmatic than in normal subjects: 304 (231--391) versus 144 (101--197). The breakfast does not interfer with the result of the TEC. In asthmatic subjects, a significant inverse correlation appears (r = 0,57, p less than 0,01) between the logarithm of TEC and the quotient: formula; see text. This correlation persists whatever may be the subject's age, the duration of the asthma or age at which he first contracted the illness. Asthma appeared after 40 years in 4 of the subjects: their TEC was higher (p less than 0,01) than in subjects who had become asthmatic before the age of forty. The respiratory function was lowered more in these 4 patients than in others who had been ill for the same time (p less than 0,001). The TEC is not related to results of skin testine with usuel inhalant allergens (grass pollen, house dust, cat's or dog's dander) or by result of a provocation test (by inhalation of allergen). Eosinophilia and bronchial obstruction are connected by one (or more) factors that may be inhalant allergens in extrinsec asthma and circulating immune complexes in intrinsec asthma.

The comparative study of the human tumor cell line HEp-2 and rat liver for the detection of antinuclear and antinucleolar autoantibodies by the indirect immunofluorescence technic in routine screening test demonstrate that, taking titer and staining pattern into account, both substrates are able to separate autoimmune disease (systemic lupus erythematosus, rheumatoid arthritis, scleroderma and primary biliary cirrhosis) patients from healthy subjects. The minimal screening test must include sera diluted 1:20 and 1:80. The capability of the HEp-2 substrate to reveal and to discriminate different speckled nuclear and nucleolar patterns explain its greater performance, notably in detecting anticentromere antibodies highly specific for the CREST syndrome and a speckled nuclear antibody frequently associated with primary biliary cirrhosis, allowing an earlier diagnosis of autoimmune diseases presenting these patterns.

Using HEp2 cells to study antinuclear antibodies has resulted in the discovery of the anti-centromere antibody which is thought to separate the CREST syndrome from progressive systemic sclerosis (scleroderma). This antibody seems to be exceptional in healthy subjects and are in patients with connective tissue diseases, except for scleroderma. It has also been found in CREST syndrome associated with other diseases, such as primary cirrhosis and neoplasias. In our study, the sensitivity of the anti-centromere antibody was 89.1% and its specificity 92.3% which shows that it is worth looking for.

One hundred and two rheumatoid arthritis patients were tested before treatment for the presence of 16 autoantibodies. Low titers of antinuclear factors appeared, but there were no antitissue antibodies. At different intervals during the treatment of a 2nd series of 176 patients, elevations of antinuclear factors were observed that correlated slightly with either autoimmune or toxic side effects. Antitissue antibodies were seen only in pemphigus and myasthenia after the onset of these complications. The practical value of systematic evaluation for autoantibodies in penicillamine-treated rheumatoid patients is questionable.

To evaluate if antimitochondrial type 5 antibodies (AMA5) might be included among antiphospholipid syndrome (APS) markers.In a retrospective study, blood variables of 48 patients with AMA5 were analyzed in relationship with clinical and biological markers of APS and systemic lupus erythematosus (SLE).We observed a high prevalence of false biological test for syphilis (95%), lupus anticoagulant (LAC) (71%), anticardiolipin antibodies (aCL) of IgG (71%) and IgM (75%) isotype, positive direct Coombs' test (54%), thrombocytopenia (52%), anti-B2 glycoprotein I antibodies (38%). Twenty-nine patients (61%) had at least one clinical manifestation of APS; 42% had recurrent arterial and/or venous deep thrombosis and 21% had recurrent fetal loss. But, for 2 patients, AMA5 were the sole detected immunological marker. Moreover, SLE was observed in 35% of the patients. These were different from 100 control patients with SLE with the respect to skin involvement and dsDNA antibodies which were less frequent (p0.01) and aCL, LAC, false biological test for syphilis (p0.001), positive direct Coombs' test and thrombocytopenia (p0.05) which were more frequent.Our data suggests (1) AMA5 is another marker of the APS (2) in patients with SLE, AMA5 seems to be a marker of a subset of SLE. This appears to justify the routine detection of these antibodies.

The sera of 131 patients with anti-liver-kidney microsome antibodies (anti-LKM) detected between 1973 and 1979 in two different laboratories were re-examined. (1) Eighty-six anti-LKM corresponded to the description given by Rizzetto, Swana & Doniach (1973), with a pattern of fluorescence predominating on the 3rd portion of the proximal tubules (P3). This group comprised 45 cases of idiopathic chronic hepatitis or idiopathic cirrhosis and one case of halothane-induced hepatitis. (2) Forty-five anti-LKM gave a different pattern on male mouse liver and male rat kidney: (a) fluorescence was greater on centrolobular than on periportal hepatocytes; (b) the first and second portions of proximal tubules (P1 and P2) predominated over P3; (c) P1 fluorescence was equally intense as P2 and (d) P3 cells were heterogeneous with one cell out of 20 more positive than the rest. Absorption tests confirmed that the corresponding antigen was also present in the liver microsomal fraction. A retrospective clinical study discovered tienilic acid-induced hepatitis in all cases. We suggest naming this new antibody 'anti-LKM2'.

A total eosinophil count (TEC) and a white blood cell count (WBCC) were performed simultaneously in 213 patients. Discrepancies were found between TEC and WBCC. WBCC did not allow detection of hypereosinophilia (TEC exceeding 300 eosinophils/microliter) in 45 patients. Patients were classified in three groups : controls (n = 27), benign disease (n = 65), and apparently cured cancer (n = 36). There was no significant difference between total eosinophil counts for these three groups (Wilcoxon non-parametric test). The incidence of hypereosinophilia (TEC exceeding 300) was similar in the three groups (11%, 14% and 6%). Average TEC levels were determined in 20 patients with decompensated hepatic cirrhosis, in 31 patients with active cancer, and in 14 patients with infection. These levels were significantly different from those found in each of the three previous groups. (Wilcoxon test). The incidence of hypereosinophilia (greater than 300/microliter) was significantly higher among patients with cirrhosis (50%) or active cancer (58%). The possible mechanisms of this hypereosinophilia and it's eventual prognostic utility are considered.

The aim of the study was to investigate the hypothesis that oral contraceptives (OC) lead to antiethinyl-estradiol antibody (AEEA) synthesis which might in turn be responsible for the thrombo-embolic complications observed in women users. The trial included 428 women divided into a) 204 healthy female volunteers as the control group (CONT), b) 139 women who had suffered thrombo-embolic accidents (THR), c) 85 women suffering from recurrent fetal loss (RFL). In each of these three categories, 50% were pill users (OC+) and 50% were not (OC-). Specific immune markers of systemic autoimmunity and anticardiolipin antibodies were looked for, as they are thought to be present in increased amounts in thrombosis or recurrent fetal loss. The AEEA prevalence differed significantly (p less than 0.05) between the CONT OC+ (32%) and the CONT OC- (13%) women. It also differed (p less than 10(-5)) between the RFL OC+ (60%) and the RFL OC- (12%) women. It did not differ between THR OC+ (36%) and THR OC- (39%) women. Within the OC+ women, the difference between the THR and the CONT groups was not found to be significant, whereas it was found to differ significantly between the RFL and the CONT groups (odds-ratio RFL/CONT estimated at 3.20, confidence interval 1.53, 6.69). Within the OC-women, the AEEA prevalence was found to differ significantly between the THR (39%) and the CONT (13%) groups (odds-ratio THR/CONT estimated at 4.40, confidence interval 2.07, 9.38%) but not between the RFL and the CONT groups.(ABSTRACT TRUNCATED AT 250 WORDS)

A case of idiopathic portal hypertension associated with connective disease resembling systemic lupus erythematosus is described. The patient was a 50-year-old woman with splenomegaly, ascites, esophageal varices, and pancytopenia, but without extrahepatic portal obstruction or cirrhosis of the liver. Electron microscopy of the liver showed perisinusoidal fibrosis. High titers of autoantibodies against proliferating cell nuclear antigen (PCNA) were found in the sera as well as in ascites; anti-DNA antibodies appeared after anti-PCNA antibodies and remained thereafter at a moderate titer. The possibility of an immunological process in the pathogenesis of idiopathic portal hypertension is discussed.

After a 10 day treatment with total adreno-cortical extract, administered to 11 subjects, the following results were obtained: increase of delayed cutaneous responses to various antigens, increase in the number of null lymphocytes, decrease in the number of B lymphocytes. These changes did not occur in 16 control patients who were not treated.