In 1940, Waalerl reported the presence of a factor in human serum which caused the agglutination of amboceptor-sensitized sheep erythrocytes. He named this factor the agglutinating activating factor and found it in the sera of 35% of 50 rheumatoid arthritis patients and 9% of 202 controls (patients with cancer, peptic ulcer, pneumonia, neurasthenia, etc). This factor was discovered in 1922, as Waaler pointed out, by Meyer,2 who, in the examination of 100,000 sera for the Wasserman reaction, found ten sera that agglutinated sensitized sheep erythrocytes. The first serum was from a patient with liver cirrhosis, and the second was from a patient with chronic bronchitis. Thus, rheumatoid factors were really first discovered in nonrheumatoid diseases.In this survey of the work of our laboratories and others, patients having possible as well as definite connective tissue diseases were omitted. The sensitizedsheep cell agglutination tests (SSC) used were either the differential-agglutination test3 or the heterophile absorbed test serum m~d i f i c a t i o n ,~~ usually the latter. The human fraction I1 (Hu FII) studies were mainly latex FII precipitation tests? although some were FII tanned sheep cell tests.5 TABLE 1 shows that the incidence of seropositive tests increases with age. Although the positive titers were generally low, some of the SSC titers in healthy donors were as high as 1 :256. One such patient had a 22s component in the serum and did not develop rheumatoid arthritis over a two-year follow-up.eIn a study done in the United States, there was a higher incidence of seropositive individuals among women and Negroes.Io It was also found that there were more seropositive individuals in Africa in those tribes that had poor nutrition.11 Rheumatoid factor is present in significant numbers of older individuals having degenerative diseases: 30% of 235 patients with an average age of 71 years (excluding those with tuberculosis, syphilis, lung disease, and sarcoidosis) were Hu FII positive; among these, 64% of those with Parkinsonism, 47% of those with diabetes mellitus, and 17% of those with arteriosclerotic cardiovascular disease were seropositive.12 TABLE 2 shows that patients may have rheumatoid factors in their sera in the course of infectious diseases. In fact, tests for rheumatoid factors have been used to help confirm the diagnosis of subacute bacterial endocarditis (SBE). Following remission of SBE in one to two months, the titers fall to zero, and it has been suggested that this is due to absence of the antigenic stimulus.24 The viral diseases studied showed 1 6 1 7 % seropositivity and include viral pneumonia, influenza, and herpes zoster; as in SBE with remission the tests became negati~e.1~ In six cases of rubella synovitis, the Hu FII tests were positive in two, and one of these was SSC positive. 14@b*39 The incidence of seropositive individuals is higher in infectious hepatitis than in any other viral disease except infectious mononucleosis.
