Beta-2 microglobulin serum levels in maintenance dialysis. What does it mean?

beta-2 Microglobulin levels (beta-2M) were analyzed at four month intervals in sera of 237 patients on various forms of dialysis over a 2 year period; twelve patients volunteered to participate in short-term kinetics studies. Duplicate beta-2M measurements in biologic fluids were performed using an RIA kit. The data presented confirm elevated serum beta-2M in dialyzed patients whatever the dialysis method used and give an overview on various factors affecting circulating serum beta-2M. Intraindividual beta-2M variations were 13% in stable ESRD patients. Unusually high values (greater than 2 SE) were observed in patients presenting with severe intercurrent disease (e.g., cancer). The only significant difference observed between groups of patients, HD (46 +/- 1 mg/L) and PD (IPD: 33 +/- 3, CAPD: 37 +/- 2 mg/L), was due to the residual renal function preserved in a higher percentage of PD patients. No significant difference was noted in HF (40 +/- 2 mg/L) and HDF (38 +/- 5 mg/L) patients, despite a higher beta-2M removal rate. beta-2M membrane permeability differs greatly among filters. It is high for AN69 and Polysulfone, intermediate for Polyamide, low for Polyacrylonitrile and none for Cuprophane. Peritoneal membrane is highly permeable to beta-2M with beta-2M dialysate/serum levels of 0.20 at the end of a 6 hr exchange. In conclusion, beta-2M determination in uremic patients is useful in assessing material permeability and biocompatibility. However, it is too early to determine the impact or the beneficial effects of using highly permeable membrane to prevent beta-2M-amyloidosis related nonarticular complications.

Genetic polymorphism of alpha 2HS-glycoprotein in a French population. Description of two new rare variants.

A French population was investigated for genetic polymorphism of alpha 2HS-glycoprotein (A2HS; nomenclature according to Human Gene Mapping 7, Los Angeles, 1983) using isoelectric focusing and immunoblotting. Three variants were observed together with two common alleles A2HS 1 and A2HS 2, whose frequencies were significantly different from the data in Canadians and Egyptians. An anodal variant to A2HS 1 was identical to a variant with two different nomenclatures reported by three different groups, indicating that there is a confusion in the A2HS nomenclature. The others were new variants with cathodal isoelectric points to A2HS 2 in the native state.

Factor I (C3b inactivator) polymorphism among five populations in Eurasia.

Factor I (C3b inactivator) polymorphism in the Japanese (in Western and Southern Japan), Taiwanese, Nepalese and French was studied using isoelectric focusing on polyacrylamide gels. The exposure of passively blotted nitrocellulose membranes to glutaraldehyde vapor facilitated the subsequent immunodetection of a low concentration of factor I and permitted the reliable identification of the three phenotypes determined by two codominant alleles FI*A and FI*B. The data indicated a west-to-east genocline, ranging from France to Western Japan, in which FI*A changed from 0.006 to 0.120.

Orosomucoid (ORM) typing by isoelectric focusing: evidence for gene duplication of ORM1 and genetic polymorphism of ORM2.

It has been demonstrated that the genetic polymorphism of human serum orosomucoid (ORM) is controlled by polymorphic ORM1 and monomorphic ORM2 loci. In this study a Japanese family was encountered in which several members had puzzling electrophoretic patterns consisting of four bands. The ORM patterns were due to the products of a duplicated ORM1 locus haplotype (ORM1 2.1) or the products of new variant alleles at the ORM2 locus. The ORM1 2.1 haplotype is very common in the Japanese population, occurring at an allele frequency of 0.16. The increased occurrence of ORM12-1 and the heterogeneity in band intensity among ORM12-1 phenotypes could be explained in terms of a duplicated gene ORM1 2.1. The ORM2 locus proved to be polymorphic, with six alleles in the Japanese population.

Immunofixation improves the detection of monoclonal gammopathy of undetermined significance (M.G.U.S.) in patients with rheumatoid arthritis.

Monoclonal gammopathy of undetermined significance (MGUS) was detected by immunofixation (IFX) in 6% of patients with rheumatoid arthritis (RA), whereas it was detected by immunoelectrophoresis in only 1% of these patients. Most of the patients with both RA and MGUS had polyclonal B cell activation, together with their monoclonal band, extra-articular features and long-lasting disease, which suggests a direct relationship between MGUS and RA status.

Combination of passive and active immunization in honeybee venom immunotherapy.

Immunotherapy with honeybee venom (HBV) is effective under optimal conditions, but many untoward systemic reactions are observed when venom doses are increased, especially with rush protocols. Although there were large interpatient variations, the levels of serum been venom specific IgG were found to significantly correlate with the protection of the allergic patients. A double-blind, placebo-controlled study was carried out to determine whether passive immunization with fractionated IgG from a beekeeper's serum pool was able to protect patients undergoing a rush immunotherapy program with HBV against untoward systemic reactions, and to observe if the active immunization with HBV could elicit an active IgG immune response toward venom allergens. Hyperimmune IgG was obtained from a pool of sera of beekeepers (Cohn fractions II to III) that was subsequently treated with pepsin for intravenous use. All IgG subclasses were found to be present in the preparation. Twenty-seven patients, highly allergic to HBV, were randomly allocated to two treatment groups. Twenty patients received 10 to 15 gm of fractionated IgG, and seven other patients received saline in a double-blind fashion. The next day, a 3-hour rush protocol attempted to reach a cumulative venom dose of 200 micrograms; 16/20 patients who received the fractionated IgG reached this dose without any systemic reaction, whereas none of the seven subjects who received saline could attain it, and all patients had a systemic reaction. The active immunization with HBV elicited a significant (p less than 0.05; Wilcoxon W Test) increase in venom IgG after 1 week of treatment in the patients who reached the maintenance dose.(ABSTRACT TRUNCATED AT 250 WORDS)

[What does circulating beta 2 microglobulin signify in uremic patients on maintenance dialysis?]. / Que signifie la beta 2 microglobuline circulante chez les urémiques en traitement de suppléance?

The authors report a 2 years prospective study on s beta 2M variations observed in a large uremic population (237 patients, 159 M, 78 F, age: 51.1 +/- 5.9 y.o.). The study consisted in two parts. A long term follow-up of s beta 2M in patients regularly treated with various dialysis modalities; hemodialysis (HD), hemofiltration (HF), hemodiafiltration (HDF), intermittent peritoneal dialysis (IPD) and continuous ambulatory peritoneal dialysis (CAPD). s beta 2M was found elevated in the overall population (41.4 +/- 10.2 mg/l) with a 12.5% variation over time observation in stable patients, not influenced by sex, causal nephropathy, and dialysis mode in anuric patients, beta 2M was inversely correlated with residual diuresis. Residual kidney function preserved longer and in a higher proportion of PD patients was the only significant fact explaining for the difference observed in s beta 2M levels between HD (46 +/- 5) and PD (33 +/- 3) patients. Intercurrent inflammatory and tumoral states increased significantly s beta 2M level in uremic patients. The short term study showed that highly permeable membranes (AN69, polysulphone) used either in HD, HF or HDF were able to decrease s beta 2M from 50 to 60%, and to remove 150 to 200 mg per session, while on the opposite HD/cuprophane increased s beta 2M from 10 to 15%. beta 2M dialysate/plasma equilibrium ratio for peritoneal membrane after a 6 hour dwelling time was 0.20, permitting a net removal of 45 +/- 4 mg/24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Orosomucoid (ORM) typing by isoelectric focusing: evidence of two structural loci ORM1 and ORM2.

Orosomucoid (ORM) phenotyping was performed by isoelectric focusing and immunoprinting. The band patterns of desialyzed ORM indicated that the ORM system is controlled by two structural loci ORM1 and ORM2. In a total of 253 samples from two Caucasoid populations, five phenotypes determined by three polymorphic alleles, ORM1*1, ORM1*2, and ORM1*3 were identified. The ORM1*3 was characteristic of the Caucasoids. The ORM2 locus was monomorphic.

Clinical and immunologic survey in beekeepers in relation to their sensitization.

Beekeepers often present allergic symptoms and represent a natural and experimental model of anaphylaxis and specific immunotherapy. Two hundred BKs were investigated. Both allergic and nonallergic subjects were selected very carefully in terms of immunologic status and exposure to bee stings. They were surveyed by a questionnaire, the titration of total serum IgE, and bee venom-specific IgE and IgG. Skin tests to HBV were performed in 176 subjects. Skin test sensitivity to HBV and allergic symptoms were significantly (p less than 0.0001) related to the estimated number of annual stings. BKs did not have allergy for more than 200 bee stings received in a year, and skin tests were negative in all cases. Many subjects who received between 50 and 200 annual stings had positive skin tests, and 9% of them had a systemic allergic history. Systemic anaphylaxis was present in 20% of BKs who received between 25 to 50 annual stings, and in 45% of BKs who are stung less than 25 times a year. Specific IgE was present in 42% of BKs whatever the number of stings received, but the titer was lower when the number of stings increased. The presence of specific IgE in subjects who are stung numerous times and who do not present allergic symptoms at the time of the stings suggests that outbreaks of anaphylaxis may be possible in nonallergic BKs. Specific IgG titrated by the Pharmacia IgG-RAST was less than 150 U/ml in most allergic subjects and over this level in most nonallergic BKs.(ABSTRACT TRUNCATED AT 250 WORDS)

Total serum IgE concentrations in adolescents and adults using the phadebas IgE PRIST technique.

Total serum IgE measured with the Phadebas PRIST technique was titrated in 117 normal non-allergic subjects, 237 allergic adolescents or adults and 89 non-allergic patients who suffered from asthma, rhinitis, or conjunctivitis. All subjects were of Caucasian origin. In normal subjects, mean total serum IgE was 38 +/- 43 kU/l. This value is exactly the same as that found in a study of Caucasian New Zealanders and very similar to the values found in most U.S. studies. This suggests that the mean total serum IgE concentration is remarkably constant in normal non-allergic Caucasians. The upper limit of the normal range is considered to be 150 kU/l. 38% of allergic patients have total IgE concentrations within the normal range. Some pollen or hymenoptera venom-sensitive patients have a total serum IgE concentration below 20 kU/l. The non-allergic patients had a mean IgE concentration of 94 +/- 93 kU/l, and 25% of them had a total serum IgE above the normal range. Asthmatic patients had higher mean IgE levels than those who were suffering from either rhinitis or conjunctivitis.

Clinical and immunological surveys in bee keepers.

Two hundred and fifty bee keepers in the South of France, working seasonally, were clinically investigated by means of a questionnaire. Forty-three per cent had presented anaphylactic symptoms and 7.0% toxic reactions when stung by bees. The personal atopic history was found to be significantly (P less than 0.01) elevated in bee keepers who experienced anaphylaxis. Total serum IgE and been venom-specific IgE were titrated in 100 subjects. Total serum IgE was significantly elevated in allergic bee keepers (P = 0.02). Although bee venom-specific IgE were significantly (P less than 0.01) higher in allergic bee keepers this parameter cannot discriminate between allergic and non-allergic bee keepers owing to a considerable overlap. Bee venom-specific IgG was assayed in seventy subjects. Their level was significantly (P less than 0.001) higher in allergic and non-allergic bee keepers as compared with non-allergic blood donors and non-bee-keeping allergic patients. In both bee keeper groups there was no difference in bee venom-specific IgG titres.

[Serum IgD levels in various dermatoses (author's transl)]. / Le dosage de l'immunoglobuline D sérique dans diverses dermatoses.

Serum IgD levels were determined by radial immunodiffusion among 349 patients with various dermatoses and 40 normal blood donnors. An increase of serum concentrations was found in atopic patients 62,5 p. 100 of which had levels over 50 mg/1 compared to 20 p. 100 in controls. No correlation was found between IgD and IgE levels in these patients. An increase (but statistically not significant) was also found in chronic urticaria whereas levels were normal in acute urticaria. No difference was found in contact dermatitis nor in psoriasis. High levels occurred in most of patients with primo-secondary syphilis and in acne pustulosa, whereas low IgD levels were found in most patients with malignant proliferative diseases (mycosis fongoide, malignant melanoma, carcinoma). However, the number of patients tested in these groups is too small to allow definitive conclusions. In our experience, determination of serum IgD values is not very useful for diagnosis in dermatologic patients.

Comparison of cord blood immunoglobulin E concentrations and maternal allergy for the prediction of atopic diseases in infancy.

Total serum IgE levels were determined in 136 newborns and their mothers and in 54 of their fathers, using the paper radioimmunosorbent test (PRIST) technique. IgE specific antibodies for house dust (Dermatophagoides pteronyssinus), orchard grass, timothy grass, and cow's milk were measured with the radioallergosorbent test (RAST). One hundred thirty-three RAST assays were negative in newborns, and in three cases RAST for cow's milk was positive. Cord blood IgE ranged from 0 to 5.5 IU/ml (mean 0.32 +/- 0.54 IU/ml); levels were significantly (p less than 0.05) higher when maternal IgE was over 100 IU/ml and when mothers had received progesterone therapy during the pregnancy. Salbutamol administration or tobacco smoking during pregnancy did not influence newborn IgE. A clinical follow-up study was conducted in 83 infants for 9 mo. Nine infants developed definite atopic disease, and possible allergic diseases were noted in eight other infants. The IgE level at birth appeared to be more predictive for the development of allergy in infancy than the family history.

Lymphocyte markers, serum thymic factor and IgE in IgA deficiency.

Eleven patients having a selective IgA deficiency had very low T-cell percentages assessed by using E-rosettes, active E-rosetts and an anti-human anti-T-lymphocyte antigen serum. B-cells were normal or slightly decreased. IgE concentrations were often low. Patients with serum IgA under 50 IU/ml often had elevated serum IgE values and low T-cell percentages. Serum thymic factor dosages were correlated with the E-rosette assay.

[Role of IgE in the study of the allergic risk of the young child (author's transl)]. / Contribution des IgE à l'étude du risque allergique chez le jeune enfant.

Cord blood IgE were determined by using the PRIST and the RAST techniques in 123 cases. The RAST assay was never positive. Total IgE were detectable in 34% of the samples; statistically increased levels were found in babies born from allergic mothers and/or when the mothers were treated with progesterone during their gestation.

Enzyme determination and RAST inhibition assays for orchard grass (Dactylis glomerata): a comparison of commericial pollen extracts.

Pollens release enzymes when they are dropped into water. Orchard Grass extracts were tested by two methods. The Api-Zym System determined 19 enzymes and colorimetric amounts of Leucine Aminopeptidases, Acid phosphatase and trypsin. These were compared with RAST inhibition assays. A good correlation was shown between the techniques. Thus the enzyme dosage may be useful for the standardization of pollen extracts.

[HLA and IgA deficiency]. / HLA et déficit en IgA.

The distribution of 29 HLA-A and B antigens was compared in 50 Caucasoïds with an IgA deficit and in 300 healthy controls. The patients were divided in 3 groups: 1) Partial selective IgA deficit (40); 2) Total selective Iga deficit (7); 3) IgA deficit associated with hypogammaglobulinemia (3). The patients viewed as a whole, we observed an increased frequency for the antigens HLA-Aw19, HLA-B5 and HLA-BW17. Yet, the modifications are not cleanly significant, with p less than 0.05, but p corrected not significant. We also considered the 3 groups separated and we did not remark any particular association with HLA. The data concerning HLA and congenital immune insufficiencies are reviewed. The most authors at once studied several immune defects. Only one Hungarian work was performed on IgA deficit. We do not confirm HLA-A1 and HLA-B8 increased frequencies, as it was reported, in Hungary, by Bajtai and al. There is no evident association between one HLA-A or B gene and the IgA deficit. The possible relation of IgA insufficiency with autoimmunity and allergy would justify complementary investigations, especially about HLA-D and Ia genes repartition in this disease.