SLE-like Syndrome Research Articles

Distribution of lymphocytes identified by surface markers in murine strains with systemic lupus erythematosus-like syndromes.

The frequencies and absolute numbers of B and T cells in the lymphoid organs of five murine strains (NZB, (NZB X NZW)F1, BXSB, MRL/l, and MRL/n) with SLE-like syndromes were examined. We assessed the frequencies of cells bearing surface Ig, C3d and IgG Fc receptors, and theta-antigen. The sequential expression of Ig isotopes on developing B cells and the Ig isotypes expressed on adult B cells were ascertained. In addition, the Ly subsets and the expression of Ia antigens coded for by the I-J subregion of the mouse H-2 complex were examined. Compared to normal, older mice, New Zealand mice had low frequencies and absolute numbers of B cells, BXSB mice had a moderate B-cell proliferation, and MRL/l mice had normal absolute numbers of B cells but a reduced frequency concomitant with a massive T-cell proliferation. Old New Zealand mice and BXSB mice had reduced frequencies and absolute numbers of T cells compared to old controls. The developmental Ig-isotype diversity during the 1st wk of age was similar in normal mice and those with autoimmune manifestations. Mature B cells were present in lymphoid organs of New Zealand mice and BXSB mice as evidenced by the high frequency of C3d receptor-bearing cells and Ig-isotype expression (high ratio of IgM- to IgD-bearing cells) in adult spleen cells. Numbers of IgG Fc receptor-bearing cells were reduced in autoimmune mice with advanced age and disease. The proliferating T cells in MRL/l mice were found to be theta-antigen positive but Ly null. These theta+-, Ly null cells may have arisen from Ly123+ T cells. MRL/l and BXSB mice seemed normal in their content of T cells bearing Ia antigens coded for by the I-J subregion of H-2. Overall, mice with autoimmune manifestations appear to express perturbations in T and B cells with development of disease, and their patterns of change vary from one strain to another.

Procainamide-induced lupus erythematosus-like syndrome in relation to acetylator phenotype and plasma levels of procainamide.

To investigate the relationship between acetylator phenotype and the development of procainamide (PA)-induced systemic lupus erythematosus (SLE-like syndrome, 28 patients with chronic ventricular arrhythmias treated with PA were followed for one year. The therapy was guided by plasma monitoring in all patients in order to obtain the proposed therapeutic plasma level of PA. Nine patients (30%), both slow and rapid acetylators, developed the SLE-like syndrome within one year. PA plasma levels were similar in both slow and rapid acetylators and there was no difference in total dose or duration of therapy before development of the syndrome. Thus, the acetylator phenotype is probably of no or minor predictive importance when PA therapy is guided by plasma monitoring. On the other hand, the antinuclear antibodies appeared significantly more rapidly in patients developing the syndrome and could possible be used as an indicator of the risk. The results support the hypothesis that the primary amino group structure of PA may be of importance in the induction of the SLE-like syndrome.

IMMUNOLOGICAL SIDE‐EFFECTS OF ANTIHYPERTENSIVE DRUGS

The immunological side-effects under treatment with antihypertensive drugs are mainly limited to autoimmunity and autoimmune disease caused by alpha-methyldopa and hydralazine. Autoimmune hemolytic anemia is more common during treatment with alpha-methyldopa. Hydralazine may induce antinuclear antibodies. Some patients develop a SLE-like syndrome. Its clinical picture is less severe and its prognosis is more favourable than that of spontaneous SLE. During treatment with low doses the disease develops exclusively in patients who are slow acetylators. It may appear also in rapid acetylators during the high dose treatment. The symptoms are usually reversible after withdrawal of the drug.

Allergy and Immunology: An Annotated Bibliography of Recent Literature

Allergy and Immunology: An Annotated Bibliography of Recent Literature

Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains.

MRL/1 and BXSB male mice have a systemic lupus erythematosus (SLE)-like disease similar to but more acute than that occurring in NZB X W mice. The common elements of lymphoid hyperplasia, B-cell hyperactivity, autoantibodies, circulating immune complex (IC), complement consumption, IC glomerulonephritis with gp70 deposition, and thymic atrophy were found in all three kinds of SLE mice. On the basis of these common elements, SLE seen in these mice can be considered a single disease in the same sense that human SLE is one disease. The differences in the SLE expressed in the different mice are no greater than those found in an unselected series of humans with SLE. However, the significant quantitative and qualitative variations in abnormal immunologic expression suggest that different constellations of factors, genetic and/or pathophysiologic, may operate in the three murine strains and that each constellation is capable of leading, via its particular abnormal immunologic consequences, to the activation of common immunopathologic effector mechanisms that cause quite similar SLE-like syndromes. From an experimental point of view, the availability of several inbred murine strains of commonplace histocompatibility types that express an SLE-like syndrome makes possible innumerable manipulations which should help to elucidate the nature and cause(s) of this disorder.

Development of Photosensitivity and an SLE-like Syndrome in a Patient With Psoriasis

An unusual case of photosensitive psoriasis and systemic lupus erythematosus-related syndrome was characterized by erythroderma, chronic urticaria, angioneurotic edema, intermittent low-grade fever, and polyarthralgias. Investigation revealed no measurable total hemolytic complement and markedly diminished levels of C4, C2, and C3. Microscopic examination of three skin biopsy sections of sun-exposed skin showed psoriasis. Skin biopsy sections of sun-exposed psoriatic plaques and of non-sun-exposed, uninvolved skin (which were stained with fluorescein-tagged anti-IgG, anti-IgM, anti-IgA, and anti-C3) showed granular deposits of IgM and C3 at the dermal-epidermal junction in the sun-exposed plaques, and IgM alone in a granular pattern at the dermal-epidermal junction in uninvolved skin. Antibodies to single-stranded but not double-stranded DNA were detected in the patient's serum. In addition, serum immune complex-like material was detected by sucrose density-gradient ultracentrifugation, standard anticomplementary assays, and radioimmunoassays using both C1q and monoclonal rheumatoid factor.

Development of photosensitivity and an SLE-like syndrome in a patient with psoriasis

Development of photosensitivity and an SLE-like syndrome in a patient with psoriasis

Association of systemic lupus erythematosus and sle-like syndromes with hereditary and acquired complement deficiency states

The most prominent association of rheumatic diseases with hereditary complement deficiency is systemic lupus erythematosus (SLE) and discoid lupus erythematosus with homozygous C2 deficiency in females. The lupus disease in these patients differ from classic lupus in 1) the increased incidence of discoid lesions, 2) the low incidence of renal disease, 3) the low or absent titers of antibodies to native DNA, and 4) the infrequent finding of immunoglobulin and complement in skin lesions. The strong positive linkage disequilibrium between C2 deficiency and HLA genes raises the possibility that genes other than those determining C2 levels may have the primary role in determining predisposition to disease in these patients. However, the finding of similar diseases in certain patients with hereditary angioedema and SLE-related syndrome who have acquired deficiency of the early components of complement supports a primary role of the C2 deficiency gene in predisposing to lupus disease in these patients.

Presence of anti-Sm reactivity in autoimmune mouse strains

The investigation of the fine specificities of antinuclear antibodies (ANAs) has been fruitful in terms of the nosology and immunopathogenesis of human autoimmune syndromes. Particular reactivities serve as "markers," in that patients with certain syndromes have a much higher incidence of such ANAs than do patients with other diseases. In this category is the almost exclusive against the nuclear acidic protein Sm. Reactivity to Sm can be detected by precipitation in agar, complement fixation, or passive hemagglutination (1,2). Autoimmune mouse strains have also provided a fertile field for the investigation of the basic phenomena of self-activity. In particular, the NZB strain and its hybrid NZB x NZW have been considered excellent models for human SLE and have therefore been studied in great detail (3,4). In addition, Murphy et al at The Jackson Laboratory, Bar Harbor, Maine, have developed several new inbred mouse strains that spontaneously develop SLE-like syndromes (5,6). These are the BXSB strain, which has a male dominant disease characterized by little antiative DNA antibody; the MRL/1, which develops massive, nonmalignant lymphadenopathy, associated with enormous increases in serum immunoglobulin levels and fulminant renal disease; and the MRL/n, which does not develop SLE-like disease until well into the 2nd yr of life, but like the MRL/1 develops high titers of ANA and fatal glomerulonephritis. The MRL/1 differs from MRL/n in only about 10 percent of its genome, including the gene responsible for the MRL/1's lymphoproliferation. In the current study, we have used the technique of double immunodiffusion (ID) in agarose with standard human reference sera (of known ANA specificity) to survey a large number of mice from the NZB x NZW, MRL/1, MRL/n, BXSB, and other strains. We report here the finding of the anti-Sm marker" antibody almost uniquely in MRL/1 and MRL/n animals. These two related strains may serve as experimental models to explore the mechanism stimulating the production of this unique autoantibody in SLE.

ANTICONVULSANT-INDUCED SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) AND NEPHROTIC SYNDROME (MS)

A 3 year old boy was treated with diphenylhydantoin (DPH), ethosuximide (E), and phenobarbital for convulsions following herpes encephalitis. After 3 months of anticonvulsant treatment he developed NS (24 hour uriae protein-9.1 grams, serum albumin-0.76 gms.%, cholesterol-356 mg.%), positive ANIF (1:800), “suspiciously” positive LE preparation, positive skin biopsy (dermalepidermal IgG), and high total eosinophil count (985 - nl 50-250)., After withdrawal of DPH and E there was gradual resolution of NS and normalization of urine, serum protein, cholesterol, ANIF and eosinophilla. Renal function and serum complement levels remained normal. Corticosteroids were not given.Although anticonvulsants have been associated with SLE-like syndromes, serologic abnormalities, nephritis or NS, no previously reported patient developed SLE and NS concurrently. The urgency in discontinuing DPH and E prevented our identifying the offending drug. It is likely that this patient sustained a syndrome of drug-induced SLE with immune-mediated reversible glomerulonephritis and NS.

Spontaneous systemic lupus erythematosus and acelylator phenotype.

Fifteen patients with spontaneous systemic lupus erythematosus (SLE) have been phenotyped by determination of plasma isoniazid (INH) half-life. Seven patients had signs of renal insufficiency. Of the 15 patients, 13 were slow and only 2 rapid acetylators. No correlation was found between the plasma INH half-lives and the renal function. Thus, there is the same marked predominance of slow acetylators in patients with spontaneous SLE as in patients with the drug-induced SLE-like syndrome.

Immunopathogenicity and oncogenicity of murine leukemia viruses. I. Induction of immunologic disease and lymphoma in (BALB-c times NZB)F1 mice by Scripps leukemia virus.

This report clearly demonstrates that a systemic lupus erythematosus (SLE)-like syndrome and lymphoma can be induced in immunologically normal (BALB/c x NZB)F(1) mice by infection of neonates with a murine leukemia virus (MuLV) (Scripps leukemia virus [SLV] 60A) isolated from NZB lymphoblasts. SLV 60A was titered in vitro (XC test) and administered to newborn and adult (BALB/c x NZB)F(1) mice over six log(10) dilutions. Propagation of MuLV in the newborn recipients was indicated by greatly elevated serum Mu gs-1 levels which were proportional to the dose of virus given. The SLE-like syndrome was characterized by antinuclear antibodies (ANA) and immune complex-type glomerulonephritis. ANA production was related to the dose of virus and reached the highest levels at 8-16 wk. The incidence of glomerulonephritis was also correlated with the dose of virus and reached nearly 50% in the animals given the highest virus dose. Both titers of ANA and incidence of glomerulonephritis were greater in females than in males, although the amounts of Mu gs-1 in sera of both sexes were equal. The incidence of direct Coombs' positivity was not significantly affected by inoculation of this virus. The incidence and time of onset of thymocytic lymphoma were linearly related to the amount of virus inoculated. High serum Mu gs-1 levels predicted lymphoma development and reflected increases in the amount of infectious virus in the spleen. No induction of tumors, autoimmunity, or high serum Mu gs-1 levels followed administration of SLV 60A to 6-wk old (BALB/c x NZB)F(1) mice or inactivated 60A or active AKR virus to newborns.

Procainamide-induced pericardial effusion

A case of hemodynamically significant pericardial effusion due to a procainamide-induced SLE-like syndrome is reported. This case emphasizes that the acute pleuropericardial syndrome seen after procainamide therapy is potentially dangerous. Close follow-up of patients taking procainamide is warranted.

Failure of procainamide to induce a systemic lupus erythematosus-like disease in animals

Procainamide induces a systemic lupus erythematosus-like (SLE) syndrome in humans. Although 77% of cardiac patients receiving the drug for 6 wk or more developed LE cells and antinuclear antibodies without clinical signs of SLE, we found no evidence that it produced similar abnormalities in animals. Seven dogs received doses as high as 588 mg/kg/day for periods up to 34 wk. Hybrid NZB NZW mice which spontaneously develop an SLE-like syndrome were treated with doses as high as 2 g/kg/mouse/day in order to determine whether the drug would aggravate the disease. There was no difference in the course or life span of 59 treated hybrids from that of the 31 littermate controls. Pilot studies were done giving large amounts of procainamide to 4 white rats, 4 guinea pigs, 1 hamster, and 1 minipig for as long as 39 wk with similar negative results. To date, drug-induced lupus has not been clearly duplicated in any animal. The failure to provoke changes in other species similar to those induced in humans suggests that there may be significant differences in etiologic factors between the animal model and human SLE. Caution should be used in implying that data obtained from lupuslike animal diseases are pertinent to humans.