Alpha-chain disease: a new immunoglobulin abnormality.

A new type of pathological immunoglobulin was found in the serum, urine, and saliva of a young Arab patient with abdominal lymphoma and diffuse lymphoplasmacytic infiltration of the small intestine. This protein is devoid of light chains and is closely related to the alpha polypeptide chains of the gamma(A1) (Le) subclass of immunoglobulin A. It is characterized by electrophoretic heterogeneity, tendency toward polymerization, and a high carbohydrate content. No intracellular synthesis of light chain was detected.

Immunochemical studies in four cases of alpha chain disease.

Studies of a number of properties of the pathological gammaA-proteins in the first four cases of the recently recognized alpha-chain disease demonstrate that, as in gamma-heavy-chain disease, the abnormal protein is devoid of light chains and represents a portion of the alpha-heavy chain related to the Fc-fragment. In two patients, serum electrophoresis showed a broad abnormal band, whereas in the two others the pathological protein was not noticeable on the electrophoretic pattern. The diagnosis of alpha-chain disease can be established without purification of the protein by immuno-electrophoresis and gel diffusion experiments using selected antisera to gammaA and a reference alpha-chain disease protein. All four proteins belonged to the alpha1-subclass, displayed electrophoretic heterogeneity, and showed a strong tendency to polymerize. The polymers occurred in vivo and were held together both by disulfide bonds and by strong noncovalent forces. Two of the three purified proteins had a very high carbohydrate content. The abnormal protein was always found in concentrated urines in variable but generally low amounts. It was not detected in parotid saliva but was present in significant amounts in jejunal fluid of all four patients. The alpha-chain disease protein was shown to be associated with the secretory piece in external secretions of two patients. The clinicopathological features were strikingly similar in the four patients. All patients were affected with a neoplastic and mostly plasmacytic proliferation involving primarily the whole length of the small intestine and the mesenteric nodes and all exhibited a severe malabsorption syndrome. While Israeli authors have emphasized the frequency of this type of abdominal lymphoma in young Arabs and non-Ashkenazi Jews, two of our patients were Kabyles, one a Syrian Arab, and one an Eurasian. Cellular studies showed that the pathological protein was synthesized by the proliferating cells in the lymphoid tissue of the digestive tract and in the mesenteric nodes, and that there was no detectable light-chain synthesis at the intracellular level.

Determination of anti-neutrophil cytoplasm antibodies (ANCA) specificity by immunofluorescence on chronic myelocytic leukemia cells.

ANCA positive sera, detected by the standard immunofluorescence method, derived from 37 patients with vasculitis were studied using formalin-acetone fixed chronic myelocytic leukemia cells (CML). All 37 sera were positive on CML cell smears. Furthermore formalin-actone fixation selectively impaired antinuclear antibody binding without reducing ANCA staining and thus facilitated differentiation of these autoantibodies which is often difficult with the standard immunofluorescence method. Two unequivocal and mutually exclusive ANCA binding patterns were identified using the CML smears: (1) type I with diffuse granular binding confined to the polymorphonuclear (PMN) cell lineage and preferentially staining immature cells; (2) type II with similar binding to the PMN cell lineage and, in addition, granular staining of the basophils. All type I antibodies were associated with a c-ANCA pattern suggesting that the major antigen recognized by these antibodies, recently identified as proteinase 3, is not detectable in basophils. The type II pattern was detected in both p-ANCA (84%) and c-ANCA (16%) positive sera. The type I sera remained positive on PMN cells from a myeloperoxidase (MPO) deficient subject and anti-MPO antibodies could not be detected in this group by ELISA. Conversely the type II pattern occurred in the presence of anti-MPO antibodies identified by immunofluorescence, ELISA and dot-blot with the exception of a single serum with antilactoferrin antibody. Type I binding only was observed in Wegener's granulomatosis (WG) but both patterns were found in microscopic polyarteritis (MPA) and rapidly progressive glomerulonephritis (RPGN).

Natural autoantibodies against the nerve growth factor in autoimmune diseases.

High titers of natural autoantibodies against the nerve growth factor (NGF) were detected in the sera of patients with systemic lupus erythematosus, autoimmune thyroiditis and rheumatoid arthritis. Autoantibodies to NGF from these pathological cases displayed higher avidity for NGF and a higher polyreactivity with certain cytoskeletal proteins and with DNA as compared to those from control human subjects. The biological activity, immunoglobulin composition and physiological relevance of these autoantibodies are discussed.

A monoclonal antibody to the HLA-A3 alloantigen.

Monoclonal antibody production recognizing the HLA-A3 antigen is described. The XI-23 antibody reacted with all of the 89 cell suspensions carrying the HLA-A3 antigen (100% cytotoxicity) among a total of 191 suspensions tested. No extra-reactivity or cross-reactivity was observed, particularly with that of HLA-A11. This antibody can thus be considered as a good HLA-typing reagent.

Anti-myeloperoxidase antibodies and associated diseases.

Thirty five (41%) sera presented anti MPO specificity, 26 of them (74%) having a p-ANCA pattern. They were present in patients with vasculitis and isolated or predominant renal involvement, but also in 24% of Wegener patients.

[Double gammopathies. Incidence and characteristics (83 cases). Clinical correlations (62 cases)]. / Gammapathies doubles. Fréquence et caractéristiques (83 cas). Corrélations cliniques (62 cas).

Within 13 years (1969-1981) 1 339 monoclonal gammopathies were recognized and fully investigated. The following were remarked: the high frequency of "double gammopathies": 6,2 p. 100 (83 cases); the high frequency of the association of (G + M): 52,4 p. 100 of double gammopathies of different classes (63 cases); both of these probably in relation of the abnormal frequency of the IgM-gammopathies (35,4 p. 100 in the Anjou province). Clinical correlation of double gammopathies do not appear to be different from those noticed in monoclonal gammopathies. In the 62 cases of obvious diagnosis, chronic lymphoproliferative diseases are the more frequent: 32,3 p. 100, followed by 17,7 p. 100 of multiple myelomas, 14,5 p. 100 of carcinoma, 4,9 p. 100 of other malignant diseases, 22,6 p. 100 of benign disorders and 8 p. 100 of idiopathic cases. In all the cases of multiple myeloma and Waldenström's macroglobulinemia, a reciprocal correlation is remarked between predominant monoclonal immunoglobulin and the diagnosis. In all the other diseases (except for 3 cases) one of the two monoclonal components is an IgM.

[Anti-centromere antibodies. Study of 67 positive sera]. / Anticorps anti-centromères. Etude de 67 sérums positifs.

From a series of 67 sera containing anticentromere antibodies we endeavoured to determine the principal clinical or biological peculiarities of these antibodies. The titers of anticentromere antibodies were usually high, with few differences between patients. Humoral immunity was frequently perturbed, with antinuclear autoantibodies (without anti-Scl 70), anti-mitochondria antibodies, rheumatoid factors, circulating immune complexes, etc. The disease predominated in women (97%) whose age and duration of symptoms varied considerably. The most frequent clinical manifestation noted in the 47 reports analyzed was Raynaud's phenomenon (93%) which in most cases (90%) was part of a complete or incomplete CREST syndrome. Telangiectasias, calcinosis and acrosclerosis were the main witnesses to the duration of these sclerodermas. Our findings were concordant with those of previous studies. However, the frequency of sicca syndrome (76%) was unexpected, and must be related to 2 laboratory results: the quasi-absence of anti-SSA and anti-SSB antibodies in our patients and the presence of two monoclonal immunoglobulins (IgM kappa and IgG lambda). There may be some degree of independence between the sicca syndrome and the sclerodermal manifestations.

[Schnitzler syndrome and Waldenström disease. Fatal outcome of the original case]. / Syndrome de Schnitzler et maladie de Waldenström. Evolution terminale du cas princeps.

The association between chronic urticaria, macroglobulinaemia and various other manifestations has been individualized as Schnitzler's syndrome. We report the terminal course of an original case followed up for 20 years, which ended as lymphoplasmocytic lymphoma with multiple sites, whereas no lymphomatous proliferation, meticulously looked for, had never been found hitherto. The lymphoma, associated with a macroglobulinaemia level above 5 milligrams, was diagnosed as Waldenström disease. Although most cases of Schnitzler's syndrome seem to follow a benign course (but the follow-up is not always long) a few cases have been reported showing evolution towards, or association with, lymphoma. This indicates that the follow-up of patients with Schnitzler's syndrome should be prolonged.

[The T-lymphocyte antigen receptor]. / Le récepteur d'antigène des lymphocytes T.

The precise knowledge of the T-cells antigen receptor (TCR) is of paramount importance; it is the first structure involved in the antigen (allergen) recognition, provided this one is presented in the right conditions; that is in the context of HLA molecules present at the surface of macrophages, after being processed inside. The TCR alpha/beta, present on more than 90% of peripheral T cells, is formed of two glyco-protein chains of similar molecular weight. The cytoplasmic end of the TCR is two short to transmit the message of recognition. The signal is transduced by neighbouring molecules forming the CD3 complex. Other membrane proteins such as CD2, LFA1, reinforce adhesion between immuno-competent cells. The presence or absence of CD4 or CD8 surface antigens, permit to distinguish two T cell subpopulations, namely helper and suppressor/cytotoxic lymphocytes. The TCR gene organization is very similar to that of light and heavy chains of immunoglobulins. Their fortuitous rearrangement explains the very large diversity of the T-cell repertoire. The TCR gamma/delta, although first appeared on the thymic cells, is present on less than 5% of peripheral lymphocytes, where its exact role is still unknown.

[The role of cytokines in allergic inflammation]. / Le rôle des cytokines dans l'inflammation allergique.

Accepting that there is "T-dependence" in the synthesis of IgE, it is certain that the cytokines, mediators that originate from activated lymphocytes, have an important role to play in allergic inflammation. The factor described by DE WECK, that assists activity of basophiles (BaPA) is identical in man with IL3, also known as Multi-CSF. Synthesis of IgE in vitro (and in vivo in mice) is dependent on IL4 and so T lymphocytes. IL5 and IL6 have a synergistic effect with the latter, though ILN gamma has an inhibitory effect. The two sub-populations TH1 and TH2 specialise, at least in mice, in the synthesis of specific cytokines the actions of which are unknown. The role of IL5 factor in the differentiation of eosinophils is shown.

[Epidemiology of monoclonal gammopathies]. / Epidémiologie des gammapathies monoclonales.

The multiple myeloma incidence rates vary from 1.5 to 4.5/100,000/year, depending on the country. Among American black people it is more than twice than among Whites. The median age is 69, with a sex ratio of 1.1. Waldenström's macroglobulinemia is 3-4 less frequent, whereas monoclonal gammapathy of unknown significance (MGUS) is much more common. Epidemiological studies in progress try to demonstrate genetic or environmental factors, in order to find means of primary prevention.

[An attempt at correlation between the numbers of intra-hepatic immunocytes and levels of serum immunoglobulins during the course of various liver diseases]. / Essai de corrélation entre le nombre des immunocytes intra-hépatiques et les taux sériques d'immunoglobulines au cours de diverses hépatopathies

Liver samples from 71 patients with various liver diseases were obtained by needle-biopsy and examined by the direct fluorescent antibody technique. Immunocytes reacting with specific conjugated anti-IgG, A, M sera were counted. An attempt to correlate i-munocytochemical observations with Ig-levels was performed but remained statistically non valid. Nevertheless, graphic comparison of data in the three homogeneous investigated groups (steatosis, cirrhosis, hepatitis) might support the view that intra-hepatic immunocytes contribute partially to enhance the serum immunoglobulin levels in liver diseases.

[Performance of reused plasma separating filters]. / Performances des filtres séparateurs de plasma réutilisés.

The performances of reused plasma separators are studied with the coefficient of filtration of IgG and IgM through the membrane and the extraction of the same immunoglobulins from the patient's plasma. 10 filters are used for 32 plasma exchanges in 6 patients. At the second use, the filter retains 78% of the initial performances. There is no more loss of the performances with the next uses. Biologic efficiency appreciated by extraction of IgG don't decrease significantly with the reuses. Those findings let us suggest the reuse of the plasma separators.

Survey of monoclonal gammopathy in western France: incidence and unexpected high frequency of IgM.

The class distribution of 4193 monoclonal gammopathies (MG), detected over approximately 10 years in western France (WF), was compared to that established by a compilation of twenty-seven series from the literature. Several points emerged from this study: the incidence of the light chain MG (4.8%) was slightly lower than commonly observed (6.0%), the number of double MG higher (4.2%) than elsewhere (1-3%) and the IgM-MG much more frequent (33.0%) than anywhere else (16.2%).