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Biomedical subjects

R E Jordon

Publications and source records attributed to R E Jordon.

At least 19 recordsLinked to original sources

Bullous pemphigoid autoantibodies reactive with intracellular basal keratinocyte antigens: studies of subclass distribution and complement activation.

Using immunofluorescence (IF) and monoclonal antibodies (MoAbs) to IgG subclasses, terminal complement components, and S-protein/vitronectin, we have extended recent observations concerning reactivity of bullous pemphigoid autoantibodies with intracellular antigens located on the polar tips of basal human keratinocytes (HuK). Using three purified bullous pemphigoid IgG fractions, autoantibody reactivity with these intracellular antigens was present in all four IgG subclasses. When skin sections were used as substrate, an identical IgG subclass distribution of autoantibodies for each bullous pemphigoid IgG fraction was observed, but reactive with the basement membrane zone. All three bullous pemphigoid IgG preparations contained IgG subclass autoantibodies capable of complement fixation. Each IgG fraction resulted in fixation of all of the terminal complement components (C5, C6, C7, C8, and C9) and assembly of the membrane attack complex (MAC) on the polar tips of basal HuK. S-protein/vitronectin was not bound in a similar fashion. Normal IgG fractions yielded consistently negative reactions. Thus, bullous pemphigoid autoantibodies, fixed to polar tips of basal HuK, are found in all four IgG subclasses and will activate complement resulting in generation of MAC.

Antibodies, Monoclonal

The surgical applications and implications of cultured human epidermis: a comprehensive review.

Replacement of skin has long been the ultimate task for surgeons facing skin-resurfacing challenges such as thermal burns and chronic ulcerations. Autologous skin grafts have been the "gold standard" for wound closure, but in patients who are massively burned, the availability of normal skin is the limiting factor. In the past 15 years the technique of in vitro cultivation of human epidermis has been developed in an attempt to deal with the problem of extensive skin loss. Although the technique is costly and arduous, grafting patients who are severely burned with cultured epidermal autografts has proved to be a life-saving measure where few alternatives exist. Cultured allografts have promoted rapid healing and pain relief in patients with chronic ulcers. Although longer follow-up is necessary, recent evidence suggests that cultured epidermis provides a wound cover that is just as durable and esthetically acceptable as conventional split-thickness skin grafts. This article reviews the development and applications of epidermal cell culture.

Animals

Comparison of three immunoassays for immune complexes in rheumatoid arthritis.

Three widely used radioassays that depend on different principles for the measurement of circulating immune complexes (CIC) in biologic fluids are the monoclonal rheumatoid factor (mRF), Raji cell, and C1q binding tests. A comparison of the ability of these methods to measure immune complex-like material in 71 sera and 30 synovial fluids of 91 patients with rheumatoid arthritis (RA) was carried out by a group working in adjacent laboratories in a single institution. The highest number of abnormal levels in the seropositive group was detected by the C1q binding assay (91%). Levels of CIC by the mRF and Raji cell tests were elevated in 81% and 76% of the patients, respectively. The closest correlation was between the Raji and mRF tests (r = 0.44 and P = 0.002) although one depends on complement fixation and one does not. Though significant correlations between the levels of CIC determined by the C1q test and either the mRF (P = 0.2) or Raji cell (P = 0.3) assay were not found in this group, 59% of the samples had elevated levels by all three tests. The frequency of CIC in the sera of patients with seronegative RA was much lower, with the C1q test again giving the highest number of abnormal results (29% versus 16% and 12% for the Raji and mRF tests). In view of the technical problems associated with these tests, particularly lack of a uniform reliable standard, it is likely that all three tests measure the same material in most RA sera and that some of the differences observed are related to inherent variability in the tests themselves rather than intrinsic differences among the CIC detected in these samples.

Adult

Concurrent linear scleroderma and systemic lupus erythematosus: a report of two cases.

Two patients with linear scleroderma (en coup de sabre) developed systemic lupus erythematosus (SLE). This association has been well documented in only one previous case. The presence of high titer antibodies to ribonucleoprotein (RNP) initially led to the diagnosis of the mixed connective tissue disease. Development of more serious clinical involvement and antibodies to Sm (case 1) or native deoxyribonucleic acid (nDNA) (case 2) helped establish a diagnosis of SLE. Use of these studies in the differential diagnosis of systemic rheumatic diseases is disucssed briefly. The presence of anti-RNAP antibodies in patients with localized scleroderma may herald a more serious rheumatic disease.

Adult

Clq binding activity in lupus erythematosus: correlation with the "lupus band test".

A 131I C1q binding assay was employed to estimate C1q binding activity (C1q BA), presumably due to the presence of circulating immune complexes, in lupus erythematosus sera. Thirteen of 16 sera from patients with systemic lupus erythematosus (SLE) had elevated C1q BA. Only 1 of 17 sera from patients with generalized discoid LE (GDLE) and none of 5 localized DLE patient's sera had elevated C1q BA. A correlation between a positive LE band test and the level of C1q BA was apparent. A positive LE band test tended to occur in patients with higher levels of C1q BA, whereas a negative LE band test tended to occur in patients with low levels of C1q BA.

Adolescent

Binding of soluble immune complexes to Raji lymphocytes. Role of receptors for complement components, C1q and C3-C3b.

We have found that, although the binding of particulate antigen-antibody complement complexes such as EAC to lymphoblastoid Raji cells is mediated largely through receptors for C3b, the binding of complement-containing soluble complexes such as those prepared with aggregated human IgG (AHG) occurs also via receptors for C1q. Evidence supporting this conclusion included: (1) Binding of AHG to Raji cells takes place after incubation in EDTA serum; (2) Binding of AHG does not occur in C1q deficient EDTA serum but does take place after addition of C1q; (3) The extent of binding of AHG in EDTA serum is a function of the amount of C1q present; (4) Raji cells can bind up to 5-4 times 10(5) molecules of 125I C1q per cell which can be blocked by unlabelled C1q; (5) AHG pre-incubated with C can bind to a T-cell line MOLT, which lacks receptors for C3b but possesses receptors for C1q to the same extent as Raji cells; (6) Immunoassays for immune complexes in human sera yield similar results whether Raji cells, MOLT cells or C1q precipitation is used for assay; (7) EAC-Raji cell rosettes can be inhibited with inulin-treated, C1q deficient serum containing C3b or C3d whereas binding of AHG or immune complexes in patient samples to Raji or MOLT cells is not inhibited by this reagent. We conclude that receptors for C1q on certain B and T lymphocytes may play an important role in physiologic functions of lymphocytes depending on binding of soluble immune complexes to their surfaces.

Antigen-Antibody Complex

Chronic urticaria-like lesions in systemic lupus erythematosus. A review of 12 cases.

Twelve of 54 patients with systemic lupus erythematosus (SLE) had nonpuric, chronic urticaria-like lessions. Skin biopsy of the lesions was performed in 11 cases, and nine showed necrotizing vasculitis. The 54 patients, in general, had severe disease, and laboratory and clinical data suggested a postivite relationship between the urticaria-like lesions and disease severity. There was no consistent relationship between the course of the urticaria-like lesions and the serologic findings and clinical activity of the SLE. The frequency and importance of urticaria-like lesions in SLE deserve further study.

Adult

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.

Adult

Circulating immune complexes in active Behçet's disease.

Levels of immune complexes (IC) were determined by the Raji-cell and C1q-binding radioimmunoassays in the sera of eighteen patients with Behçet's disease. Eight patients (44%) were found to have significantly elevated levels of IC (range 56 to 1600 microgram equivalent aliquots of heat aggregated IgG (AHG/ml) by the former test and nine by the latter (7 to 500 microgram equivalent AHG/ml). The presence of IC showed a significant correlation with disease activity score (P = 0.003, Mann-Whitney Rank Sum Test). Abnormal values of IC tended to remain abnormal when sera were retested after 1 year. There was no correlation between IC and duration of disease or any specific organ involvement. The IC were found predominantly in fractions of about 19S and greater when fractionated by sucrose density gradient or Sephadex column techniques. The results suggest the possibility that IC may contribute to the pathophysiology of Behçet's disease.

Adult

Separation of epidermis from dermis with sodium thiocyanate.

After human skin is treated with 2 N sodium thiocyanate, epidermis is easily separated from dermis. The level of cleavage occurs at the lamina lucida of the basement membrane zone. Bullous pemphigoid antigen remains attached to the epidermis.

Histological Techniques

Immunopathology of cicatricial pemphigoid: studies of complement deposition.

Immunopathologic investigations were conducted on the sera and oral mucosal tissue specimens of 23 patients with cicatricial pemphigoid. A linear, continuous basement membrane zone pattern was noted in 83% of oral mucosal biopsy specimens studied. This pattern is indistinguishable from the pattern noted in immunofluorescence studies of bullous pemphigoid, herpes gestationis, and some cases of desquamative gingivitis. Complement studies provided data supportive of classical pathway activation in cicatricial pemphigoid tissue. Deposition of IgA with Factor B, properdin, and C3 raised the possibility of alternative pathway activation, a question requiring further study. Circulating antibasement membrane zone antibodies were noted in the sera of two patients with cicatricial pemphigoid.

Basement Membrane