Objective. To determine the range of antinuclear antibodies (ANA) in “healthy” individuals compared with that in patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc; scleroderma), Sjögren's syndrome (SS), rheumatoid arthritis (RA), or soft tissue rheumatism (STR). Methods. Fifteen international laboratories experienced in performing tests for ANA by indirect immunofluorescence participated in analyzing coded sera from healthy individuals and from patients in the 5 different disease groups described above. Except for the stipulation that HEp‐2 cells should be used as substrate, each laboratory used its own in‐house methodology so that the data might be expected to reflect the output of a cross‐section of worldwide ANA reference laboratories. The sera were analyzed at 4 dilutions: 1:40, 1:80, 1:160, and 1:320. Results. In healthy individuals, the frequency of ANA did not differ significantly across the 4 age subgroups spanning 20–60 years of age. This putatively normal population was ANA positive in 31.7% of individuals at 1:40 serum dilution, 13.3% at 1:80, 5.0% at 1:160, and 3.3% at 1:320. In comparison with the findings among the disease groups, a low cutoff point at 1:40 serum dilution (high sensitivity, low specificity) could have diagnostic value, since it would classify virtually all patients with SLE, SSc, or SS as ANA positive. Conversely, a high positive cutoff at 1:160 serum dilution (high specificity, low sensitivity) would be useful to confirm the presence of disease in only a portion of cases, but would be likely to exclude 95% of normal individuals. Conclusion. It is recommended that laboratories performing immunofluorescent ANA tests should report results at both the 1:40 and 1:160 dilutions, and should supply information on the percentage of normal individuals who are positive at these dilutions. A low‐titer ANA is not necessarily insignificant and might depend on at least 4 specific factors. ANA assays can be a useful discriminant in recognizing certain disease conditions, but can create misunderstanding when the limitations are not fully appreciated.

We have performed the first controlled study of colchicine in acute gout, to determine its efficacy and toxicity, and to define the natural history of acute gout. Two-thirds of colchicine-treated patients improved after 48 hours, but only one-third of the patients receiving placebo demonstrated similar improvement. The colchicine-treated patients responded earlier; significant differences from placebo were shown after 18-30 hours. All patients given colchicine developed diarrhea after a median time of 24 hours (mean dose of colchicine 6.7 mg). This side effect occurred before relief of pain in most patients.

We have tested the extent of immune selftolerance to the ubiquitously expressed nuclear/cytoplasmic (5), and contains species-specific epitopes (6). These studies are consistent with molecular mimicry (7) or "altered self' (8) acting as an initiating event ultimately leading to antigen-driven autoimmunity. However, it is unclear how these mechanisms could lead to simultaneous targeting of the La and Ro autoantigens in Sjogren syndrome (2) or result in the specific subsets of anti-nuclear antibodies associated with other autoimmune disorders (1). La is an ATP-dependent (9) transcription-termination factor for RNA polymerase III (10) that binds the 3' uridine-rich region of polymerase III RNA transcripts (11). At least two Ro polypeptides have been identified: 52-kDa Ro and 60-kDa Ro (Ro60). The function of the Ro proteins is undefined; however, it is known that Ro6O associates with the Y RNAs (cytoplasmic small RNAs) (12) and, at least transiently, with the La molecule (13,14). Thus it is possible that the occurrence of autoantibodies to both La and Ro in autoimmune disease is a consequence of their structural association intracellularly (2).We have examined whether immunity to La and Ro6O autoantigens can be triggered by immunization with recombinant antigen in normal, healthy mice. The data indicate incomplete immune tolerance to the La and Ro autoantigens after immunization of normal mice and show that initiation of immunity to a single component of the La/Ro RNP complex is sufficient to trigger autoantibodies reactive with other components of this complex.

This paper describes the survival rates of 763 rhesus monkeys maintained at the Yerkes Regional Primate Research Center (YRPRC). The survival rates were determined by methods used to calculate survival rates of human populations. The monkeys were divided into 3 groups based on their specific life histories. Group I monkeys were wild-born and were housed singly from the time they came into captivity at about 2 years of age. Group I1 monkeys were born either in the wild or in captivity and were housed in social groups since their acquisition at ages 2 to 8 years. Group I11 monkeys were born at the YRPRC and housed in social groups. Due to these differences in life histories, direct comparisons among survival curves of the 3 groups are, at best, tenuous, as are comparisons with populations maintained at other facilities. In the present study the highest mortality rate occurred during the first month of life. The maximum life span attained in our group I was 35 years, with only 6.2% of monkeys in this group attaining an age beyond 30 years.

Summary: Spreading of the immune response is a common theme in organ‐specific and systemic autoimmune diseases. We evaluated whether some of the mixed antinuclear antibody patterns characteristic of systemic autoimmunity might be the result of determinant spreading from a single initiating event. Immunisation of healthy mice with individual protein components of the La/Ro ribonudeoprotein (RNP) targeted in systemic lupus erythematosus and primary Sjögren's syndrome induced autoanti‐bodies recognising Ro60 (SS‐A), Ro52 (SS‐A) and La (SS‐B) and in some cases the molecular chaperones calreticulin and Grp78. The endogenous antigen(s) driving determinant spreading might be derived from physiological apoptosis which could explain the involvement of some chaperone proteins in the autoimmune response. Diversified anti‐La/Ro antibody responses were initiated by challenge with a single subdominant T epitope of La even though some self epitopes of La were efficiently tolerised. The pattern of autoantibody responses in primary Sjögren's syndrome was strongly influenced by HLA class II phenotype which we speculate controls activation of T cells recognising defined peptides from the La/Ro RNP In t his way, HLA class II alleles may be critical in influencing initiation and spreading of systemic autoimmune reactions. Molecular mimicry of such determinants by exogenous agents might readily initiate spreading of an autoimmune response in genetically susceptible hosts.