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A distinguishing feature of the mixed connective tissue disease (MCTD) syndrome is the presence in the serum of antibody in high titer to ribonucleoprotein (RNP). To determine whether this was an exclusive observation, a large rheumatic disease population was surveyed for the presence of antibody in high titer to extractable nuclear antigens (ENA) including RNP. Of 650 sera examined, 440 (from 240 patients) had antinuclear antibody. Only 39 patients had serum antibody to ENA in titers ≧ 1:200 dilution. In 16 the anti‐ENA was shown by RNAse digestion to be anti‐RNP. Although many clinical and laboratory characteristics were similar in these two groups, the patients more closely resembled the previously described MCTD syndrome and, importantly, less often had severe renal and central nervous system disease manifestations. Thus the presence of serum antibodies to ENA that are predominantly RNAse‐sensitive (anti‐RNP) helps to identify a rheumatic disease syndrome and also appears to have prognostic value.

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Evidence is presented that serum from rats with adjuvant arthritis stabilizes the membranes of isolated normal rat liver lysosomes. The stabilizer retarded the release of the lysosomal enzymes, acid phosphatase and p-glucuronidase, but not the release of the mitochondria1 enzyme, isocitric dehydrogenase. Stabilizing activity in serum paralleled adjuvant disease, being greatest when the inflammation was most intense and subsiding as the arthritis diminished. Activity could be removed from the serum by absorption with isolated membranes; adjuvant arthritis serum did not inhibit enzyme activities. The membrane reactant was neither a corticosteroid nor an antibody but was a large molecular weight substance with charge properties similar to an a-globulin.The contents of the subcellular organelle, the lysosome, are related to the development and evolution of the inflammatory reaction (1, 2).. Leukocyte degranulation and lysosomal labilization lead to vasodilatation, edema (3-5), tissue disintegration and chemotactic accumulation of additional leukocytes (6), thus tending to perpetuate the inflammatory reaction. Since the inflammatory response to many different stimuli is self-limited and since the lysosome is intimately involved, it seemed possible that a substance limiting the participation of lysosomes in inflammation could appear in the Submitted for publication June 18, 1971; accepted September21,1971. course of the reaction. Such a substance, by preventing subsequent lysosome involvement, would interrupt the inflammatory process.Adjuvant arthritis in the rat, an intense selflimited inflammatory disease, served as a model for these studies (7). T h e data to be presented in this paper indicate that a circulating, nonsteroidal, large molecular weight substance arises in the course of this experimental disease. This substance reacts with lysosomal membranes to retard the release of their lytic contents. MATERIALS AND METHODS Animals and the induction of adjuwnt arthri-tis. Male rats* were housed randomly in single cages in a room maintained at 23.5' f 0.5" C with a regular schedule of artificial lighting from 0600 to 1800 hours, alternating with darkness. The animals were fed Purina Chow and tap water ad libitum. Rats weighing 140-160 g were injected with 0.1 ml of heavy mineral oil containing killed M butysicum, 6 mg/ml, intradermally in a hind foot pad. Control animals received injections of mineral oil only. Animals were observed daily for the development of arthritis in joints of the noninjected extremities. The arthritis score was deHoltzman Farms, Madison, Wisc. 144Arthritis and Rheumatism, Voi. 15, No. 2 (March-April 1972) LYSOSOME STABILIZATION termined by summing the products of individual joints involved times the relative intensity of inflammation (0-4+) in each joint. Extra-articular manifestations of this disease were not included in the arthritis score. In early experiments, single animals were bled from the tail at varying intervals throughout the course of the disease; their sera were stored froze...