Treatment of mixed cryoglobulinemia with recombinant interferon alpha and adjuvant therapies. A prospective study on 20 patients.

In order to evaluate the efficacy of interferon alpha (IFNa) in mixed cryoglobulinemia (MC), a prospective multicenter clinical trial was conduced in April 1992. It consisted of treating 20 clinically symptomatic MC patients with IFNa for 26 weeks. Hepatitis C virus (HCV) infection was detected in 16 patients.

Interleukin-6 serum levels in patients with multiple myeloma.

Studying the prognostic value of serum interleukin-6 (IL-6) levels in multiple myeloma, we observed important daily variations in some patients. Therefore a unique serum IL-6 measurement should be interpreted with caution and requires confirmation by multiple determinations performed over a period of several days.

Schnitzler's syndrome associated with sensorimotor neuropathy.

We describe a patient with chronic urticaria in association with monoclonal IgM gammopathy (Schnitzler's syndrome). Seven years after the onset of the cutaneous lesions sensorimotor neuropathy developed. Myelin-associated glycoprotein was detected in the patient's serum.

Childhood-onset systemic lupus erythematosus: antiphospholipid antibodies in 37 patients and their first-degree relatives.

Objective: Antiphospholipid antibodies (aPL) are noted with increased frequency in patients with systemic lupus erythematosus (SLE). The main manifestations found to be associated with aPL are arterial and venous thrombotic events, thrombocytopenia, and recurrent pregnancy loss. This study is an attempt to define the incidence of aPL in patients with childhood-onset SLE and in their relatives and to correlate their presence with clinical manifestations, and especially, to evaluate the risk of thrombosis in aPL-positive subjects.

Characterization of a human monoclonal autoantibody directed to cardiolipin/beta 2 glycoprotein I produced by chronic lymphocytic leukaemia B cells.

We determined the specificity and sequence of immunoglobulin molecules synthesized by monoclonal B cells from a patient with chronic lymphocytic leukaemia (CLL) who presented with a number of clinical and biological autoimmune symptoms. Heterohybrids obtained by fusion of CLL cells with the mouse X63-Ag 8.653 myeloma produced IgM lambda MoAbs directed to the cardiolipin/beta 2 glycoprotein I (beta 2GPI) complex and ssDNA.

Nucleotide sequence analysis of the VL and VH domains of five human IgM directed to lamin B. Evidence for an antigen-driven process in the generation of human autoantibodies to lamin B.

Objective: To gain insight into the genetic origin of human antilamin autoantibodies, we determined the nucleotide sequence of the light and heavy chain variable region (VL and VH) domains of 5 IgM antibodies directed to lamin B. These antibodies represent a distinct subset of antinuclear antibodies, and their presence is associated with a particular lupus-like syndrome.

Methods: We derived and cloned lymphoblastoid cell lines from peripheral blood B cells of 3 patients, selected anti-lamin B-producing subclones, and sequenced the messenger RNA coding for Ig heavy and light chains.

Lupoid sclerosis with antiphospholipid and antimyelin antibodies.

Lupoid sclerosis is a rare syndrome associating clinical symptoms of multiple sclerosis (MS), positive false tests for syphilis and positive tests for antinuclear and anticardiolipin antibodies. In a patient with lupoid sclerosis, antimyelin antibodies were detected by indirect immunofluorescence on human sciatic nerve sections. These antibodies were not found in the serum of control patients with MS nor in sera of patients with antiphospholipid autoantibodies and focal ischemic neurologic disease.

Characterization of two human monoclonal IgM antibodies that recognize nuclear lamins.

Using immunofluorescence and immunoblotting techniques, we have identified monoclonal IgM lambda from two patients that are specific for lamins A and C and lamin B, respectively. Lamins A, B, and C are peripheral membrane proteins of the nuclear envelope with structural similarities to cytoplasmic intermediate filament proteins. When studied by indirect immunofluorescence on rat tissues, the serum containing anti-lamin B IgM stained smooth and striated muscles in addition to nuclear envelopes.

Frequency of central lesions in polyneuropathy associated with IgM monoclonal gammopathy: an MRI, neurophysiological and immunochemical study.

CNS lesions were studied in polyneuropathy associated with IgM monoclonal gammopathy. Eleven out of 12 patients with IgM MGUS and one patient with Waldenstrom's disease had clinical and electrophysiological features indicating a demyelinating polyneuropathy. MRI showed CNS white matter lesions in two cases.

Anti-lamin-B autoantibodies in a patient with cold urticaria.

Anti-lamin-B autoantibodies at a significant level had been found on two occasions in the serum of a 56-year-old woman who was suffering from an apparently idiopathic chronic cold urticaria. Anti-lamin autoantibodies can be detected in various autoimmune disorders including hepatitis, vasculitis and peripheral blood cytopenia. In our patient, there was no other clinical or biological abnormality.

Human autoantibodies to lamin B receptor are also anti-idiotypic to certain anti-lamin B antibodies.

Autoantibodies reactive with nuclear envelope proteins are mainly detected in human sera from patients with liver diseases. Some of these antibodies are directed to lamin B, lamins A and C, or to the lamin B receptor (LBR). We show here that the latter one are anti-idiotypic to certain anti-lamin B antibodies.

Changes in serum immunoglobulin patterns in adults with common variable immunodeficiency.

Striking variations of serum immunoglobulin class and IgG subclass levels were observed in five patients with common variable immunodeficiency. They occurred mainly in untreated patients or, in those patients who received substitutive therapy, could not be merely due to replacement. They result in major changes in the immunoglobulin deficiency patterns, such as a shift from profound hypoimmunoglobulinaemia to IgA/IgG2/IgG4 deficiency or to isolated IgG2 deficiency.

A novel 43-kDa glycoprotein is detected in the nucleus of mammalian cells by autoantibodies from dogs with autoimmune disorders.

We have characterized a new antibody specificity in a panel of sera from dogs developing systemic lupus erythematosus (SLE) or clinically related autoimmune disorders. This antibody stains in a speckled fashion the nucleus of cells of different mammalian origins. The target antigen is a basic (pI 9.

Antinuclear antibodies directed to a 200-kilodalton polypeptide of the nuclear envelope in primary biliary cirrhosis. A clinical and immunological study of a series of 150 patients with primary biliary cirrhosis.

Antinuclear antibodies giving a perinuclear fluorescence and directed to a 200-kilodalton polypeptide of the nuclear envelope have been described in primary biliary cirrhosis. The purpose of this study, based on a series of 150 patients with primary biliary cirrhosis, was to ascertain the prevalence of these antibodies and to compare patients with and without these antibodies. Antinuclear antibodies giving a perinuclear fluorescence were demonstrated in 43 of the 150 patients (29%); antibodies directed to the 200-kilodalton polypeptide of the nuclear envelope were found in 40 of these 43 patients.

Autoantibodies to lamins in rheumatoid arthritis.

The presence of autoantibodies reacting with lamins A and C was demonstrated in sera from 2 patients with rheumatoid arthritis (RA). One patient developed antilamin antibodies several years after being diagnosed as having RA; she was also found to have chronic active hepatitis. The second patient had severe nodular RA.

C4 null alleles in childhood onset systemic lupus erythematosus. Is there any relationship with renal disease?

C4 genotyping was performed in 38 unrelated patients with systemic lupus erythematosus (SLE) aged 2-16 years at onset. Null alleles were found in 68% of patients. Ten patients had one null allele at the C4A locus and 11 others had one null allele at the C4B locus.

Reactivity of human monoclonal IgM with nerve glycosphingolipids.

We examined the reactivity of monoclonal IgM of sera from patients with neuropathy and monoclonal IgM, with or without antibody activity to myelin-associated glycoprotein (MAG), as well as sera from non-neurologic patients with Waldenström's macroglobulinaemia, with various nerve glycolipids extracts or with purified gangliosides. As expected from previous studies, all (five cases) anti-MAG IgM stained two glycolipids, the chemical characteristics of which corresponded to sulphated glucuronyl-paragloboside (SGPG) and sulphated glucuronyl-lactosaminyl-paragloboside (SGLPG). Five of 12 sera from patients with neuropathy whose IgM was devoid of anti-MAG reactivity stained nerve extracts greatly enriched (98%) with SGPG and SGLPG.

Characterization of human autoantibodies specific for lamin A.

We have characterized human autoimmune polyclonal antibodies reactive with lamin A, a 74 kDa peripheral protein of the nuclear envelope. Unlike other known antibodies to lamin A, the antibodies described here do not crossreact with the structurally related lamin C. These antibodies feature only chi light chains suggesting that their specificity is restricted to a limited number of epitopes.

[Serum antibodies in dogs with autoimmune disorders recognize 40 kd glycoprotein in the nucleus of mammalian cells].

We report a new antibody specificity in 15 sera recovered from a group of dogs developing systemic lupus erythematosus (SLE) or clinically related disorders. This antibody stains in a speckled fashion the nucleus of human Hep-2 cells. Immunodiffusion tests with saline extracts of rabbit thymus showed that all 15 sera generate a common precipitation line which crosses the lines from reference sera to Sm, SS-A/ro, SS-B/La, and RNP antigens.

[Peripheral neuropathy and plasmocytic proliferations. Apropos of 17 cases].

Seventeen cases of peripheral neuropathy with plasmocytic proliferation were grouped together to analyze the clinical manifestations and evolution of this association of symptoms. The plasmocytic proliferation was 5 times that of multiple myeloma, 9 times that of a solitary bone plasmacytoma and 3 times that of a solitary plasmacytoma. The follow-up lasted 1 to 18 years (mean, 8 years) for solitary plasmacytomas.