Alveolar macrophages from subjects infected with HIV-1 express macrophage inflammatory protein-1 alpha (MIP-1 alpha): contribution to the CD8+ alveolitis.

A human monoclonal anticardiolipin autoantibody (ACA) of the IgA-k isotype, designated 185/12, is described. The antibody was prepared from peripheral B cells, obtained from a patient with a history of habitual abortion, by immortalization with Epstein-Barr virus (EBV). The antibody displays a strong binding activity to cardiolipin and phosphatidyl L-serine, but not to phosphatidylcholine, phosphatidylinositol, ssDNA and dsDNA. It binds to cardiolipin in a concentration-related and saturable manner (Kd = 3.0 x 10(-8) M). This reaction is dependent upon the presence of bovine serum, and is fully inhibited by cardiolipin vesicles. The 185/12 antibody exhibits different binding patterns to the solid-phase bound cardiolipin-serum complex and to its individual components (cardiolipin and bovine serum). The Bmax of 185/12 binding to the complex (0.968 OD units) is higher than the sum of the Bmax values calculated for each one of the complex components (0.352 + 0.179 = 0.531 OD units). Bovine serum as well as purified beta 2-glycoprotein I (beta 2-GPI) in suspension inhibit the binding of 185/12 to the complex. 185/12 binding capacity increases in direct relation to the rising concentration of beta 2-GPI. Collectively, these data may be interpreted to suggest that 185/12 antibody, which is an IgA isotype, exhibits characteristics usually attributed only to antiphospholipid autoantibodies (APA) of the IgG isotype, that are associated with the clinical spectrum of APA syndrome (APA-S). It is, therefore, possible that autoantibodies of the IgA isotype could play a pathogenic role, which may be different from that of the IgG isotype, in the development of autoimmune phenomena.     

Altered synthesis of interferon-γ and expression of interferon-γ receptor by peripheral blood mononuclear cells from patients with IgA nephropathy and non-IgA proliferative glomerulonephritis

Previously we reported disease-specific interaction between interferon- (IFN-) and interleukin-4 (IL-4) in patients with IgA nephropathy (IgAN), suggesting the existence of unusual T cell behavior in this disease. In the present study, we investigated characteristic synthesis of interferon- (IFN-) and expression of IFN- receptor (IFN-R) in the peripheral blood mononuclear cells (PBMC) from patients with IgAN and other chronic proliferative glomerulonephritis (PGN). Heparinized peripheral blood samples were obtained from 38 patients with chronic mesangial proliferative glomerulonephritis (CGN; including 24 with IgA nephropathy) and 20 healthy controls. PBMC were isolated by gradient centrifugation and fragments were cultured in Iscove's modified Dulbecco's medium (IMDM) supplemented with 10% fetal calf serum (FCS) for 72 hr. IFN- concentrations in supernatants were evaluated by the enzyme-linked immunosorbent assay (ELISA). Other parts of PBMC pellets were reacted with anti-human IFN-R monoclonal antibody and FITC-labeled anti-mouse second antibody for analysis of IFN-R expression on these cells by FACScan. The remaining PBMC were fractionated into CD4⁺ T cells, CD8⁺ T cells, B cells, NK, cells and macrophages using the MACS cell sorting system. The isolated cells were evaluated for IFN- or IFN-R mRNA expression by the semiquantitative RT-PCR method.In vitro IFN- synthesis was enhanced in patients with CGN, and NK cells were revealed to be responsible for such enhancement. On the other hand, the expression of IFN-R on macrophages was suppressed in CGN patients. These results suggest that impairment of regulation of the IFN- system might be involved in the development of CGN.     

Synergistic convergence of microbiota-specific systemic IgG and secretory IgA

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Competitive inhibition enzyme immunoassays for the measurement of human IgG, IgA and IgM

Competitive-inhibition enzyme immunoassays for the measurement of human IgG, IgA and IgM are described. These assays can be readily performed with commercial antisera and a recently developed method for purifying human IgA and IgM with high yield. The assays described are specific, with undetectable (<0.5%) cross-reactivity between the immunoglobulin classes in all systems, except with purified IgM, which cross-reacted to 1.9% with the IgG enzyme immunoassay.Minimal detectable concentrations of 2.5±0.8 ng/ml for IgG 4.2±0.9 ng/ml for IgA and 7.2±1.4 ng/ml for IgM were recorded, indicating that these assays are particularly sensitive. There is little within-assay variation (mean coefficient of variation = 3.9%), although the between-assay variation was substantially greater (mean coefficient of variation = 23.5%). These assay systems appear to be particularly suited to the measurement of immunoglobulin production by lymphocytes in culture. In such studies the assay must be specific, sensitive and be capable of discriminating between levels of immunoglobulin produced in response to various experimental treatments.     

Ontogenesis of the secretory immune system and innate defence factors in human parotid glands

Immunoglobulin-producing cells and epithelial expression of secretory component (SC), amylase, lysozyme (Ly) and lactoferrin (Lf) were studied by immunohistochemistry to obtain information about the development of mucosal immunity. Tissue specimens were obtained from 20 fetal and 40 postnatal parotid glands. (1) Fetal specimens. Occasional IgM- and IgA- but no IgD-, IgG- or IgE- producing cells were seen (ratios, IgM:IgA:IgD:IgG:IgE approximately 4:1:0:0:0). The IgAl subclass dominated (median 90%, range 50-95%) and these cells were mostly J-chain-positive (median 97%, range 94-98%). Only few IgA2-producing cells were seen (median 10%, range 5-50%) and they were also mostly J-chain-positive (median 99%, range 98-100%). Amylase, Ly and Lf were most prominent in early fetal life, while only small amounts of SC were present. (2) Postnatal specimens. Secretory component increased markedly along with a growing number of IgA- and IgD-producing cells (IgA:IgM:IgD:IgG:IgE approximately 4:2:1:1:0). The IgAl subclass remained predominant (median 65%, range 50-90%) although the proportion of IgA2-positive cells tended to be raised (median 35%, range 10-50%). Most IgAl (median 97%, range 67-100%) and IgA2 (median 94%, range 75-100%) cells were J-chain-positive. These features probably reflected local activation of the immune system in response to environmental factors. The amount of amylase, Ly and Lf decreased shortly after delivery, perhaps because the cellular stores were emptied by postnatal increase in secretory activity.     

Naturally occurring human IgA autoantibodies against IgE-DES myeloma protein

The prevalence and specificity of naturally occurring human IgA anti-IgE autoantibodies (a-E Ab) were studied by ELISA with anti-IgA monoclonal antibodies (mAb) and a purified myeloma IgE as solid-phase protein, i.e., IgE-DES(κ). Such detected IgA a-E Ab were common among adults, and significantly increased geometric means (GM) were found in patients with atopy (P= 0.006; n= 41; GM = 79.3 arbitrary units (AU)/ml) and filariasis (P= 0.02; n= 41; GM = 75.9 AU/ml), as compared with nonatopic controls (n= 42; GM = 48.8 AU/ml). No such difference was observed between age-matched nonatopic (n= 22; GM = 36.7 AU/ml) and atopic (n= 22; GM = 38.6 AU/ml) children. Children had significantly (P= 0.001) lower IgA a-E Ab concentrations than adults, probably as a result of age, because IgA a-E Ab concentrations and age of children were significantly correlated (n= 44; P<0.05; r_s= 0.30). IgA a-E Ab concentrations were very low in cord serum (n= 32; median <0.1 AU/ml). Sex did not influence IgA a-E Ab concentrations in any study group. The specificity of IgA a-E Ab in nine sera was studied by ELISA inhibition assay using IgE-DES myeloma as solid-phase protein and inhibitory proteins of the IgG, IgM, IgD, and IgE classes, including five different IgE myeloma proteins, as well as three enzymatic fragments of IgE-DES. The inhibitions indicated that all IgA a-E Ab tested reacted in a low-affinity reaction with determinants restricted to IgE-DES, i.e., the solid-phase protein. These epitopes were heat-resistant (2 h; 56°C) and located in the Fab_?-DES fragment. No isotype-specific IgA a-E Ab were found because none of the four other IgE proteins were inhibitory. Subclass typing indicated that most IgA a-E Ab belonged to the IgA 1 subclass. It is unlikely, for reasons of restricted specificity, low affinity, and common prevalence, that such IgA 1 a-E Ab are connected with IgE-mediated disorders. The study also raises questions on the definition of anti-IgE antibodies.     

过敏性哮喘患者鼻分泌液中分泌性IgA含量的测定

本文对２６例过敏恶性性支气管哮喘患者鼻分泌液中ＳＩｇＡ含量等进行了超速离心检测，结果表明：患者鼻分泌液中ＳＩｇＡ，ＩｇＡ，总ＩｇＡ含量均较正常人明显增加（Ｐ＜０．０５，＜０．０１，＜０．０５）。ＩｇＡ对白蛋白的相对分泌系数与正常人无明显差异（Ｐ＜０．０５）。结合其它研究认为过敏性哮喘患者呈粘膜ＳＩｇＡ免疫高反应状态。     

Aberrant T-regulation in rheumatoid arthritis and IgA nephropathy affects CD5+ and CD5- B lymphocytes equally.

T-suppressor function and T-helper function in healthy adults, elderly patients with non-immune diseases, and patients with rheumatoid arthritis (RA) and IgA nephropathy (IgAN) were titrated by adding graded concentrations of CD8+ cells to autologous CD8-depleted peripheral blood mononuclear cells (PBMC), or CD4+ cells to CD8- 4- PBMC, respectively. Following culture with pokeweed mitogen (PWM), numbers of CD5+ and CD5- immunoglobulin-secreting cells were determined using a combination of rosetting with anti-CD5-coated Dynabeads and reverse haemolytic plaque formation (Jones, 1990). Of 11 RA patients studied, eight had slightly reduced suppressor activity for CD5+ and CD5- IgM-secreting cells, and three with active disease and high serum levels of C-reactive protein, could not suppress IgG, IgA or IgM secretion by either B subset. Helper activity for both CD5+ and CD5- B cells was slightly but significantly increased in RA patients. One of eight patients with IgAN could not suppress IgG, IgA or IgM production by CD5+ or CD5- B cells, and all IgAN patients required strikingly fewer CD4+ cells for PWM-induced activation of CD5+ and CD5- B cells than controls. It was concluded that in two immunologically mediated diseases in which some patients have raised numbers of circulating CD5+ B cells, aberrant T-regulation affects CD5+ and conventional CD5- B cells equally.     

Intense training: mucosal immunity and incidence of respiratory infections

This investigation examined the impact of a multistressor situation on salivary immunoglobulin A (sIgA) levels, and incidence of upper respiratory tract infection (URTI) during the French commando training (3 weeks of training followed by a 5-day combat course). For the URTI, the types of symptoms were classified according to the anatomical location of the infection. Saliva samples were collected (8 a.m.) from 21 males [21 (2) years] before entry into the commando training, the morning following the 3 weeks of training, after the 5-day combat course, and after 1 week of recovery. sIgA, protein and cortisol concentrations were measured. Symptoms of URTI were recorded during the study from health logs and medical examinations. After the 3 weeks of training, the sIgA concentration was not changed, although it was reduced after the 5-day course [from 120 (14) mg l^–1 to 71 (9) mg l^–1, P<0.01]. It returned to pre-training levels within a week of recovery. The incidence of URTI increased during the trial (²=53.48; P<0.01), but was not related to sIgA. Among the 30 episodes of URTI reported, there were 12 rhino-pharyngitis, 6 bronchitis, 5 tonsillitis, 4 sinusitis and 3 otitis. Cortisol levels were raised after the 3-week training (P<0.01), dropping below baseline after the combat course (P<0.01). Stressful situations have an adverse effect on mucosal immunity and incidence of URTI. However, the relationship between sIgA and illness remained unclear. The large proportion of rhino-pharyngitis indicated that the nasopharyngeal cavity is at a higher risk of infection.