The following clinical and pathologic features were evaluated in 170 patients with electron microscopically documented membranous glomerulopathy: age, sex, race, American Rheumatism Association lupus criteria, serum ANA, serum complement, glomerular hypercellularity, stage of subepithelial dense deposits, endothelial tubuloreticular inclusions, tubular basement membrane deposits, tissue ANA, glomerular deposition of IgG, IgM, IgA, C3, C4, and Clq. At the time of biopsy 148 patients had no clinical evidence for lupus, and 22 had a clinical diagnosis of lupus. Six additional patients eventually developed overt lupus after an average of 12 months. Incidences of serologic and pathologic features in lupus as compared with nonlupus membranous glomerulopathy were determined. These data were used to calculate sensitivity, specificity, positive and negative predictive values, and overall efficiency of each parameter in differentiating between lupus and nonlupus membranous glomerulopathy. In general, serologic, morphologic and immunohistopathologic features are more accurate at ruling out lupus than making the diagnosis of lupus. However, a number of features are significantly more frequent in lupus membranous glomerulopathy. Therefore, identification of these features, especially more than one, warrants a high suspicion of lupus rather than nonlupus membranous glomerulopathy even in patients without clinically overt systemic lupus erythematosus. The positive/negative predictive values of some of the pathologic features studied are as follows: mesangial dense deposits 63/99, subendothelial dense deposits 77/93, tubuloreticular inclusions 61/96, intense C1q deposition 47/95, tubular basement membrane deposits 100/87, and glomerular hypercelularity 26/86.

The purpose of this investigation was to study the formation and origin of basal lamina and anchoring fibrils in adult human skin . Epidermis and dermis were separated by "cold trypsinization ." Viable epidermis and viable, inverted dermis were recombined and grafted to the chorioallantoic membrane of embryonated chicken eggs for varying periods up to 10 days . Basal lamina and anchoring fibrils were absent from the freshly trypsinized epidermis before grafting although hemidesmosomes and tonofilaments of the basal cells remained intact. Basal lamina and anchoring fibrils were absent from freshly cut, inverted surface of the dermis . Beginning 3 days after grafting, basal lamina was noted to form immediately subjacent to hemidesmosomes of epidermal basal cells at the epidermal-dermal interface . From the fifth to the seventh day after grafting, basal lamina became progressively more dense and extended to become continuous in many areas at the epidermal-dermal interface . Anchoring fibrils appeared first in grafts consisting of epidermis and viable dermis at five day cultivation and became progressively more numerous thereafter . In order to determine the epidermal versus dermal origin of basal lamina and anchoring fibrils, dermis was rendered nonviable by repeated freezing and thawing 10 times followed by recombination with viable epidermis . Formation of basal lamina occurred as readily in these recombinants of epidermis with freeze-thawed, nonviable dermis as with viable dermis, indicating that dermal viability was not essential for synthesis of basal lamina . This observation supports the concept of epidermal origin for basal lamina . Anchoring fibrils did not form in recombinants containing freeze-thawed dermis, indicating that dermal viability was required for anchoring fibrils formation . This observation supports the concept of dermal origin of anchoring fibrils .

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A specific interleukin-1 (IL-1) receptor antagonist (IL-lra) was used to examine the roles of IL-1 in an experimental model designed to analyze the reactivation phase of erosive arthritis, induced in rats with peptidoglycan-polysaccharide polymers (PG-APS) isolated from cell walls of group A streptococci. Monoarticular arthritis was initiated by injection of a small dose of PG-APS into an ankle joint, and reactivation was induced by intravenous injection of PG-APS 20 days later. Human recombinant IL-lra given at a dose of 2 to 3 mg/kg at the time of reactivation of arthritis and at 6-h intervals inhibits the increase in joint swelling by at least 60%. Joint swelling is suppressed 30 to 50% when the initial treatment with IL-lra is delayed until 6 h after reactivation. IL-lra is not effective when the initial injection is delayed 12 or 24 h. With an injection schedule of IL-lra given at the time of reactivation and every 6 h, treatment can be stopped at 24 h and the suppression of swelling is no different from that in rats for which injections are continued for 4 days. The results indicate that IL-1 has a prominent, although not exclusive, role in initiating inflammation in this model and is involved in the amplifying processes in progressive inflammation and chronic erosive disease. An antiinflammatory function of IL-1 is also indicated from data showing that IL-Ira treatment limited to 6 h or less after the induction of reactivation enhances joint swelling, whereas intravenous injection of human recombinant IL-113 24 h before reactivation suppresses the reactivation of arthritis.

Arthritis is often associated with intestinal diseases, but the etiology is not known. We developed a rat model whereby arthritis was reactivated by experimental small bowel bacterial overgrowth (SBBO). Self-limited, monoarticular arthritis was induced by intra-articular injection of 2 g of rhamnose peptidoglycan-polysaccharide derived from group A streptococci into the ankle joints in female Lewis rats. Eleven days after intra-articular injection, when swelling was resolving, experimental SBBO induced by surgical creation of jejunal self-filling blind loops reactivated arthritis, but SBBO induced by creation of self-emptying blind loops, which minimally increases luminal bacteria, and sham operation did not (P < 0.001). Increased joint diameters in rats with self-filling blind loops persisted for at least 56 days after surgery. Reactivation of arthritis due to SBBO was prevented by anti-tumor necrosis factor alpha antiserum and interleukin 1 receptor antagonist (P < 0.001), indicating that these cytokines mediate joint swelling secondary to intestinal injury. Recombinant bactericidal/permeability-increasing protein, an agent which neutralizes endotoxin, and metronidazole, which is active against anaerobic bacteria, prevented arthritis (P < 0.001), but polymyxin B (which also neutralizes endotoxin) and gentamicin had no effect. Mutanolysin, an enzyme which degrades peptidoglycan-polysaccharide from group A streptococci, exacerbated arthritis for the first 6 days but then diminished joint swelling from 12 to 21 days after surgery (P < 0.001). These studies introduce a reproducible animal model of reactivation of arthritis secondary to intestinal injury and demonstrate a role for bacterial products from endogenous enteric organisms.