ABSTRACT
Utilizing a newly perfected multiple-response permutation procedure, we analyzed the autoantibody titer of systemic lupus erythematosus (SLE) patients during active and convalescent periods of disease, SLE patients without neurological involvement, and three other comparison groups (patients with active tuberculosis, patients with multiple sclerosis, and healthy normal controls). The multidimensional analysis we used distinguished those SLE patients with neurological involvement from the other SLE patients. Differences were noted by a univariate analysis measuring antibodies to single- and double-stranded DNA, poly (G), Sm, RNP, Ro, La, and gangliosides. Elevated concentrations of the common anti-DNA idiotype 16/6 were also noted among SLE patients with neuropsychiatric illness. This report stresses that increased disease activity in SLE patients with neuropsychiatric phenomena is reflected by their autoantibody profile.
Subject(s)
Autoantibodies/blood , Lupus Erythematosus, Systemic/complications , Nervous System Diseases/blood , Neurocognitive Disorders/blood , Antibodies, Antinuclear/immunology , Antigens, Nuclear , Cardiolipins/immunology , DNA/immunology , Data Interpretation, Statistical , Diagnosis, Differential , Evaluation Studies as Topic , Histones/immunology , Humans , Nervous System Diseases/epidemiology , Nervous System Diseases/etiology , Neurocognitive Disorders/epidemiology , Neurocognitive Disorders/etiology , Nuclear Proteins/immunology , Poly G/immunology , Poly I/immunology , Polynucleotides/immunology , Predictive Value of TestsABSTRACT
Sera of 16 patients with systemic lupus erythematosus (SLE) and active involvement of the CNS were examined for the presence of antibodies to human brain neurons, using indirect immunofluorescence of human brain tissue sections. Thirteen of the 16 patients (81%) had high antineuronal titers, which declined during convalescence, compared with 18 of 105 (17%) SLE patients who had no CNS disease. Competition assays showed that the binding of the antineuronal antibodies was blocked by mycobacterial glycolipids and bovine brain extracts. This finding suggests an additional link between mycobacterial infection and SLE.
Subject(s)
Antigens, Bacterial/immunology , Autoantibodies/analysis , Lupus Erythematosus, Systemic/immunology , Mycobacterium/immunology , Neurons/immunology , Adult , Antibodies, Antinuclear/analysis , Cells, Cultured , Cross Reactions/physiology , Female , Fluorescent Antibody Technique , Humans , MaleABSTRACT
One hundred sixty-four sera samples of patients with malignant diseases were analyzed for the presence of autoantibodies to ssDNA, dsDNA, poly(I), Poly(G), cardiolipin, histones, RNP, Sm, Ro(SSA), and La (SSB). No distinction could be made between these patients and a comparative group composed of age-adjusted healthy subjects when measuring antibody levels to these autoantigens by the ELISA technique. This finding remained valid after further subgrouping of the patients according to age, sex, and histologic origin of the tumor. The authors conclude that in contrast to the known clinical coexistence of neoplasia in autoimmune states, there is no increased incidence of antinuclear autoantibodies in malignant conditions.
Subject(s)
Autoantibodies/analysis , Neoplasms/immunology , Adolescent , Adult , Aged , Antibodies, Antinuclear/analysis , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle AgedABSTRACT
The sera of 46 patients with multiple myeloma were examined for the presence of anti-tuberculosis (TB) glycolipids antibodies. In positive sera samples, anti-polynucleotides, anti-histones, anti-cardiolipin, anti-Sm and anti-RNP activities were sought. Antibodies against three different mycobacterial glycolipids were detected in 10 of the 46 sera. Three (P429, P557, P5) showed high titres of antibodies against all three different TB glycolipids. Of the 10 reactive samples, two antibodies were purified (P429, P557). P557 reacted with various polynucleotides and other antigens tested (Sm, RNP, cardiolipin, histones). One immunoglobulin (P207) which showed high activity against Sm and RNP had no activity against TB glycolipids and was employed as a control. The cross-reactivity between mycobacterial glycolipids and the nuclear antigens was further established by bi-directional competition assays with P429 and P557. Our study shows a high incidence (22%) of anti-TB glycolipids antibodies in sera of patients with monoclonal gammopathies, some of which show anti-DNA and other anti-nuclear antigens activities. This is additional evidence for the mycobacterial-nuclear antigen cross-reactivity which may suggest a possible role of infection (e.g., tuberculosis) in autoimmune diseases.
Subject(s)
Antibodies, Bacterial/immunology , Antibodies, Monoclonal/immunology , Multiple Myeloma/immunology , Mycobacterium bovis/immunology , Nuclear Proteins/immunology , Phosphatidylinositols/immunology , Antibodies, Antinuclear/immunology , Antibodies, Bacterial/analysis , Antigens, Nuclear , Autoantigens/immunology , Binding Sites, Antibody , Binding, Competitive , Cardiolipins/immunology , Cross Reactions , Histones/immunology , Humans , Phosphatidylinositols/pharmacology , Polynucleotides/immunology , RNA, Small Nuclear/immunologyABSTRACT
We have studied 44 sera of patients with uveitis, and controls for the presence of ANF and other antinuclear antibodies (ss-DNA, ds-DNA, Poly (I), Poly (G), RNP, Sm, histones) and for the presence of a common anti-DNA idiotype (16/6 Id) employing the ELISA method. Various incidences of antinuclear antibodies were found in sera of patients with uveitis. The uveitis specimens were found to have high titers of autoantibodies to ss-DNA, ds-DNA, Poly (I), histones and Poly (G). High titers of anti-Sm antibodies were detected only in 9% of the uveitis patients, which is markedly lower than the reported percentage of anti-Sm antibodies in SLE. No significant differences were found in the incidence of antinuclear antibodies between sera of patients with localized uveitis and uveitis concomitant with a systemic disorder. Similarly, no relationship was found between location of uveitis (anterior versus posterior) and autoantibody profile. Our results imply that despite considering uveitis as a specific organ malady, it should be regarded serologically as an autoimmune condition.
Subject(s)
Antibodies, Antinuclear/analysis , Autoantibodies/analysis , Uveitis/immunology , Antibodies, Antinuclear/immunology , Autoantibodies/immunology , Enzyme-Linked Immunosorbent Assay , Humans , Reference ValuesABSTRACT
The binding of human lupus anti-DNA antibodies and murine anti-mycobacterial antibodies to human cortical brain tissue sections was assessed by the indirect immunofluorescent technique. Prior adsorption of the reactive monoclonal antibodies on nuclear extracts, ss-DNA, synthetic polynucleotide polymers, histones, mycobacterial glycolipids, and bovine brain extracts abrogated the monoclonal antibodies' binding to the brain. Intermediate blocking activity was conferred also by ribonucleic components as RNP, Ro(SSA), and La(SSB). Specificity to neuronal tissue was demonstrated by failure of non-neuronal tissue extracts to abolish antibodies' reaction to the cortical tissue sections in competition assays. The anti-TB and anti-DNA antibodies seemed to compete on their binding to a common neuronal membranal epitope. These results indicate that mycobacteria share antigens with DNA and human brain tissue. Furthermore, these data support the concept that anti-DNA antibodies may play a pathogenetic role in SLE patients with neuropsychiatric involvement via crossing of a "leaky" blood brain barrier and attachment to brain tissue components.
