Peter Barland

The effect of normalization of serum complement and anti-DNA antibody on the course of lupus nephritis: a two year prospective study.

A prospective study was carried out in 25 patients with systemic lupus erythematosis (SLE) on the effect of normalizing serum complement (CH50) and anti-DNA antibodies on the course of lupus nephritis. In 16 of the 25 patients, CH50 was maintained within the normal range for two years. Urinary protein excretion increased or remained low in all 16. Repeat renal biopsies were performed in 10 of these 16, and disclosed either stabilization of glomerular disease or diminution. In the nine patients in whom CH50 could not be normalized with tolerated doses of drugs, urinary protein excretion increased or remained increased. Repeat renal biopsies in six of these nine patients were carried out and showed worsening of glomerular disease in five. No clear-cut correlation was found between urinary protein excretion or renal disease and the serum levels of anti-DNA antibody. We conclude from these observations that continuous normalization of CH50 by drug therapy in patients with SLE is associated with stabilization or diminution of lupus nephritis.

A novel cutaneous vasculitis syndrome induced by levamisole-contaminated cocaine

In order to describe the clinical and serologic features of a cutaneous vasculitis due to cocaine contaminated with the adulterant levamisole, we report four new cases of this syndrome along with 12 previously reported cases identified through a PubMed Literature search (1964 to March 2011). Of the 16 patients described, the average age was 43, with a female predominance (81% of patients). Over half of patients had involvement of the earlobes, and the rash frequently affected the extremities in a “retiform” pattern. Leukopenia or neutropenia was reported in 56% of patients. Ninety-three percent were anti-neutrophil cytoplasmic antibody positive, and 63% tested positive for anti-phospholipid antibodies. The predominant pattern seen on histopathological examination of the skin was small vessel vasculitis and/or a thrombotic vasculopathy. Treatment in these patients varied widely, with several patients showing improvement or resolution of the rash without specific therapy following cessation of illicit drug use. This new cutaneous vasculitis syndrome can be recognized by its characteristic rash and skin pathology, together with leukopenia and autoantibody production. Certain clinical features can be attributed to the adulterant levamisole, though cocaine as well may play a role in its pathogenesis.

The incidence and clinical significance of antibodies to extractable nuclear antigens.

AbstractSera from 378 patients were assayed for antibodies to extractable nuclear antigens (ENA), ribonucleoprotein (RNP) and nonnucleoprotein (Sm). Anti-ENA antibodies were not found in control subjects, patients with rheumatic diseases and negative fluorescent antinuclear antibodies (FANA), or in patients with rheumatoid arthritis, dermatomyositis, drug-induced lupus, idiopathic thrombocytopenic purpura (ITP), or hemolytic anemia with positive FANA. Anti-Sm antibodies were found in 32 per cent of patients with systemic lupus erythematosus (SLE) and were not found in any other condition. There were no significant clinical or serological differences between patients with and without anti-Sm antibodies. Anti-RNP antibodies occurred in 15 per cent of SLE patients, 9 per cent of scleroderma patients, and in 100 per cent of patients with mixed connective tissue disease. SLE patients with anti-RNP antibodies had a significantly lower anti-DNA antibody titer and a significantly lower incidence of nephritis and impaired renal function. Anti-Sm and anti-RNP titers did not vary with changes in clinical status. Awareness of the presence of anti-Sm and anti-RNP antibodies is diagnostically useful. Anti-RNP antibodies have a prognostic value as well.

Effect of long-term normalization of serum complement levels on the course of lupus nephritis

PURPOSE We compared the long-term outcome of patients with lupus nephritis in whom normalization of complement levels (CH50) was sustained by adjustment of immunosuppressive therapy to those patients with persistently low complement levels despite similar immunosuppression in whom therapy was adjusted solely on the basis of clinical disease activity. PATIENTS AND METHODS Thirty-nine female patients with lupus nephritis recruited from 1972 to 1979 were prospectively studied (mean follow-up, 116.7 +/- 11 months). Entry criteria included initial renal biopsy, low CH50, and elevated anti-DNA antibody levels. A second biopsy was performed in 24 patients after an interval of 40.6 +/- 5 months. Treatment was started with prednisone (1 mg/kg/day). Azathioprine at a dose of 1.5 to 2.0 mg/kg/day was added if complement was not normalized by prednisone alone. Twenty-five of 39 patients had normal complement levels within six months (Group 1), and immunosuppressive therapy was tapered but continuously readjusted to the lowest dosage that preserved normal CH50 and maintained clinical remission. Eight of these 25 patients subsequently became persistently hypocomplementemic due to inadequate drug intake (Group 1B), whereas the complement levels continued to be controlled in the other 17 patients (Group 1A). Despite similar therapy, the remaining 14 patients did not achieve normalization of complement within the initial six months of therapy, and therefore future treatment decisions were based solely on clinical symptoms (Group 2). Renal pathologic lesions were classified according to World Health Organization criteria and a semi-quantitative chronicity index. RESULTS During the first six months, there were no significant differences in clinical or histologic features between patients in whom complement levels were controlled and patients in whom complement levels were not controlled. After a mean observation period of 10 years, however, patients with consistent normalization of complement (Group 1A) did much better than patients with only short-term complement control (Group 1B) or persistent hypocomplementemia (Group 2). Both groups with low complement levels had a similar outcome with significantly worse kidney and patient survival. Life-table analysis demonstrated that the differences in outcome between complement-controlled and complement-uncontrolled groups became apparent only after five or more years of follow-up. Patients with a low chronicity score on initial biopsy whose complement level was controlled did uniformly well with no renal failure or death. (ABSTRACT TRUNCATED AT 400 WORDS)

Psychologically Distinguishable Groups of Rheumatoid Arthritis Patients: A Controlled, Single Blind Study

&NA; Systematic measures of mood and psychological symptoms were obtained for 68 ambulatory arthritis patients on two standard questionnaires, the Brief Symptom Inventory (BSI) and the Profile of Mood States (POMS). We studied two groups of rheumatoid arthritis patients, one positive and the other negative for rheumatoid factor and erosive joint changes. A third group of patients had other forms of arthritis. All were matched for chronicity and functional impairment as well as psychosocial background variables. We found a distinct psychometric response profile that allowed us to sort patients into the three clinical groups with an accuracy ranging from 63% to 100%.

Studies of surface membranes of two mouse fibroblast cell lines

Abstract The proteins and glycoproteins of whole mouse fibroblast surface membranes were examined by polyacrylamide gel electrophoresis. Membranes derived from two mouse cell lines exhibiting different growth behavior and cells at different stages of growth were compared. A new method for isolation of intact whole surface membranes from small numbers of cultured cells was utilized. The distribution of membrane proteins after polyacrylamide gel electrophoresis was determined by staining the gels or labeling the membranes with radioactive leucine and assaying sequential slices of the gel for radioactivity. No differences were seen between patterns derived from the membranes of the two cell lines, or between those of cells at different stages of growth. Membrane glycoproteins were labeled with radioactive glucosamine and their distribution determined. The glycoprotein patterns of the two cell lines were similar, but differed from the protein patterns significantly.

Combined Autoimmune Disease in a Patient with AIDS

Abstract Immune dysregulation in HIV-infected patients, along with the new medications for treatment of AIDS that possess immunomodulating potential, may lead to an increased incidence of autoimmune diseases in this patient population. However, the presence of combined autoimmune diseases in an AIDS patient is rare. Relapsing polychondritis (RP) is an uncommon inflammatory disease manifested by recurrent attacks of auricular chondritis. The presence of type II and IX collagen antibodies, and their association with HLA-DR4 and other autoimmune diseases, suggests that antiself reactions may be present. Sarcoidosis is a granulomatous disease manifested by inflammation of the lungs, eyes and joints. In the peripheral blood there is depressed cellular immunity and enhanced humoral immunity. We here describe a case of coexisting RP and sarcoidosis in an AIDS patient.

Diagnosis of lupus nephritis by skin immunofluorescence, in the absence of extrarenal manifestations of systemic lupus erythematosus

Six patients with glomerulonephritis were found to have granular deposits of complement and/or immunoglobulins at the dermalepidermal junction of normal skin. No patient had extrarenal clinical manifestations of systemic lupus erythematosus (SLE). The only serologic test suggestive of SLE was a positive antinuclear antibody (ANA) reaction; results of complement and antinative deoxyribonucleic acid (DNA)-antibody tests were repeatedly normal. The patients with glomerulonephritis had a favorable initial response to therapy with prednisone with or without azathioprine. These patients may represent a variant of SLE in which the diagnosis can only be established by a direct immunofluorescence test of normal skin. Alternatively, they may constitute a separate new clinical entity. Because of the favorable response to therapy, we suggest that skin immunofluorescence be performed in patients who present with unexplained glomerulonephritis and a positive ANA.

Triad of glomerulonephritis, antinuclear antibodies, and positive skin immunofluorescence: Variant of systemic lupus erythematosus

We are reporting findings in 13 patients who presented with glomerulonephritis without evidence of systemic disease, but who were found to have positive antinuclear antibody results and immunoglobulin and/or complement deposits at the dermal-epidermal junction of normal skin not exposed to light. There was no evidence of other organ involvement, and serologic tests for systemic lupus erythematosus (SLE) gave negative results. The renal disease is characterized by severe proteinuria, focal or diffuse proliferative glomerular lesions on biopsy, with variable patterns of immunoglobulin deposits. No clinical manifestations or serologic results typical of SLE have developed during prolonged observation. HLA phenotyping carried out in eight of the 13 patients revealed DR2 or DR3 alloantigens or both in seven of the eight patients, an incidence similar to that in patients with overt SLE. Because of the specificity of the skin biopsy immunofluorescence, the similarity of HLA-DR antigens, and a favorable response of the renal disease to therapy, we believe that these patients have a variant of SLE.