Demonstration Of Immune Complexes Research Articles

Microangiitis in lupus-induced pulmonary hemorrhage.

The authors describe four patients with systemic lupus erythematosus (SLE) and massive pulmonary hemorrhage in whom open-lung biopsies showed a distinctive small-vessel vasculitis. This lesion is characterized by acute inflammation and necrosis involving capillaries, arterioles, and small muscular arteries and is termed microangiitis to reflect the small size of the affected vessels. The involvement of capillaries is manifested by an infiltrate of necrotic neutrophils within alveolar septa often associated with destruction of the alveolar wall. This capillaritis was present in all cases, while involvement of arterioles and small arteries was seen in three. Immunofluorescence and electron microscopy demonstrated immune complexes in only two. The finding of acute microangiitis in a lung biopsy from a patient with pulmonary hemorrhage should suggest the diagnosis of SLE, and it may be a more reliable diagnostic feature than the demonstration of immune complexes.

Demonstration of Immune Complexes Containing the Ribonucleoprotein Antigen Ro in Primary Biliary Cirrhosis

We have previously demonstrated circulating and tissue-fixed immune complexes containing the small cytoplasmic ribonucleoprotein antigen Ro and immunoglobulin G (IgG) in a case of sicca syndrome associated with primary biliary cirrhosis. To establish the overall prevalence of such complexes in liver disease, we performed dissociation experiments under conditions of Ro antigen excess. Of the diseases tested, Ro-containing immune complexes were restricted to cases with primary biliary cirrhosis. Sera from 29 of the 47 patients with primary biliary cirrhosis (60%) showed IgG-containing immune complexes; 10 of the 29 sera samples (34%) positive for IgG-containing immune complexes exhibited immune complexes composed of Ro and anti-Ro IgG. These complexes sedimented predominantly as intermediate or large aggregates and were encountered most frequently in cases with extra-hepatic features.

Ethambutol-Induced Toxic Epidermal Necrolysis

Toxic epidermal necrolysis (TEN) is a severe cutaneous reaction that most commonly is related to drug exposure and that clinically can be confused with other bullous dermatoses, particularly staphylococcal scalded skin syndrome (SSSS) and erythema multiforme major (the Stevens-Johnson syndrome). We report the first case, to our knowledge, of TEN associated with ethambutol hydrochloride administration. Toxic epidermal necrolysis can be partially differentiated from other bullous dermatoses by history and clinical presentation. Microbiological results (eg, the isolation of Staphylococcus aureus in SSSS) and immunological studies (eg, the demonstration of immune complexes in the Stevens-Johnson syndrome) may aid in differentiation, but ultimately the diagnosis depends on histopathological examination of involved skin.

Demonstration of Immune Complexes in Thrombotic Thrombocytopenic Purpura and Effect of Exchange Transfusion

A 30‐year‐old man with clinical and laboratory features of thrombotic thrombocytopenic purpura (ITP) underwent exchange transfusion with 9 units of whole blood over a 24‐h period. Then, the neurological, renal, and haematological manifestations resolved and the patient recovered completely. Serial plasma samples were obtained before and at 8 h intervals during the exchange transfusion. A convalescent plasma sample was obtained 14 and 80 d later. Immune complexes were demonstrated in the pre‐exchange transfusion plasma, by polyethylene glycol (PEG) gradient sedimentation, separated by electrophoresis and analysed immunochemically. There were shown to be light, medium and high molecular weight sedimentation zones in the PEG gradients. The medium zone consisted of immune complexes containing platelet membrane asrociated antigens and IgG antibody; the heavy and light zones only showed the presence of IgG. There was progressive clearance of these zones by the exchange transfusion with the convalescent specimens showing a marked decrease in all zones, especially those of the middle molecular weight (which on analysis represent true immune complexes). The clearance of these immune complexes from the circulation by exchange transfusion could explain the clinical response seen in the patient.

Erythema multiforme: demonstration of immune complexes in the sera and skin lesions.

In twenty patients with erythema multiforme we investigated circulating immune complexes and their deposition in the skin lesions. CIq-binding activity was elevated in ten of twenty patients, and the platelet aggregation titre was high in three of twelve tested sera. Decreased levels of C3 were seen in two and of C4 in one out of eighteen patients. Direct immunofluorescence showed a deposition of C3, IgM or IgG in the blood vessel walls of the upper dermis in four of twelve patients. These findings may suggest that transient production of circulating immune complexes and their deposition play an important role in the pathogenesis of this disease.

Demonstration of Immune Complexes in Spontaneous and Histamine-Induced Lesions and in Normal Skin of Patients with Leukocytoclastic Angiitis

Clinical and laboratory observations have strongly suggested that leukocytoclastic angitis is an immune complex disease. Since immune complexes can be visualized as electron-dense deposits by electron microscopy (EM), this method was used in conjunction with direct immunofluorescence (IF) to determine whether complexes could be demonstrated in spontaneous lesions, and in uninvolved skin in which the vessels were made permeable by the local injection of histamine. Histamine-induced wheals were produced in the uninvolved skin of patients with active angitis. In the resulting wheal, EM studies revealed electron-dense deposits characteristic of immune complexes in postcapillary venules and direct IF studies demonstrated complement and immunoglobulins in the vessel walls. Neutrophils in varying stages of disintegration were present thereby reproducing the histopathologic changes of spontaneous lesions. EM and IF studies of nonmanipulated uninvolved skin also revealed electron-dense deposits and immune reactants in the vessel walls. Neutrophils were not present, however. This observation indicates that immune complexes are deposited in vessels before tissue damage ensues. Study of spontaneous lesions older than 24 hr revealed only fibrin by EM and no immune reactants by direct IF. In spontaneous lesions less than 24 hr old, electron-dense deposits and fibrin were seen by EM, and complement and immunoglobulins by IF. Histamine-induced wheals should be a useful device to investigate patients with disorders that have an immune complex pathogenesis.

Polymyositis and cell-mediated immunity.

Polymyositis has usually been included with the connective-tissue diseases because of certain well recognized clinical and laboratory overlaps. However, aside from the demonstration of immune complexes in muscle-vessel walls, particularly in childhood dermatomyositis,1 evidence for an immunologic mechanism for the tissue injury has in most patients been sparse. Hypergammaglobulinemia, if present, is usually modest, hypocomplementemia is rare, and there is no renal involvement. It is for these reasons that a number of investigators have in recent years explored the possibility that a cellular immune mechanism is responsible for the muscle injury that characterizes this disease. From these studies has come . . .

ANTIGEN-ANTIBODY REACTIONS IN JEJUNAL MUCOSA IN CHILDHOOD CŒLIAC DISEASE AFTER GLUTEN CHALLENGE

Immunofluorescence studies, using unfixed sections to demonstrate immune complexes, were carried out before and after gluten challenge on the jejunal mucosa of thirteen children with treated cœliac disease and one child in whom this diagnosis had been excluded. Positive staining was seen in the region of the basement membranes of villous and crypt epithelia in ten of the thirteen patients, and the immunoglobulin involved was IgA. Parallel histological and ultrastructural studies confirmed that after gluten challenge morphological changes occurred in the lamina propria of these ten patients and that the onset of these changes coincided with the demonstration of immune complexes by immunofluorescence techniques.