Immunoglobulins and complement components in synovial fluid of patients with acute rheumatic fever.

Three components of complement and six other serum proteins were assayed in synovial fluid and serum samples from 25 patients with acute rheumatic fever in Trinidad. The resulting data indicate a relative decrease in both early and late components of complement within the synovial fluids which suggests local activation by immune complexes. Such activation of complement within the joint spaces may play a primary role in development of the inflammatory arthritis of acute rheumatic fever.

Changing types of nephritogenic streptococci in Trinidad.

The relation of seven different M types of streptococci to acute glomerulonephritis associated with skin lesions in South Trinidad has been studied by means of type-specific antibody assays as well as by isolation and identification of the strains. The data indicate that, one after another, five of these strains have prevailed among patients with acute glomerulonephritis during the past five years. At least three of the strains (M-types 55, 49, 57, and/or 60) were associated with epidemic increases in nephritis cases. The appearance of five consecutively predominant types of nephritogenic streptococci during a relatively short period of time is in contrast to the continuing prevalence of M-type 12 strains among nephritogenic streptococci primarily associated with respiratory infections in temperate zones. These observations suggest that the skin sores commonly found on children in tropical Trinidad, provide a particularly suitable environment for development of nephritogenic types. It remains to be seen whether these types will recur or whether new types will continue to emerge in Trinidad.

Streptococcal neuraminidase and acute glomerulonephritis.

We examined the hypothesis that streptococcal neuraminidase may alter host serum immunoglobulin G so that autoantibodies are formed which lead to immune complexes and acute glomerulonephritis. We confirmed the observation that T-type 4 and T-type 12 streptococci (both associated with acute glomerulonephritis) are the most likely of many types studied to produce neuraminidase. However, we did not find this enzyme to be produced by any of 23 streptococcal strains isolated from patients with nephritis, whereas it was produced by two strains from patients with rheumatic fever and by one strain from a patient with scarlet fever. Also, we were unable to find direct or indirect evidence of increased neuraminidase activity in the sera of six patients with acute glomerulonephritis when they were compared with the sera of six patients with acute rheumatic fever and with those of six normal subjects.

Serum immunoglobulin A and antibody to M-associated protein in patients with acute glomerulonephritis or rheumatic fever.

Serum immunoglobulin A (IgA) was markedly increased in 80% of 50 patients with acute rheumatic fever in Trinidad in contrast to 20% of 63 patients with acute glomerulonephritis, whereas serum IgG was increased in nearly all of both groups. Since total antibody to M-associated protein (MAP) (assessed by complement fixation) is the only antibody as yet consistently found to be of higher titer in patients with acute rheumatic fever than in patients with acute glomerulonephritis in Trinidad, it was measured and the titers were related to serum levels of IgA. The titers of total antibody to MAP were greater than or equal to 40 in 58% of the rheumatic fever patients, 43% of the nephritis patients, and 8% of well school-children. However, its presence in rheumatic fever patients did not correlate directly with amounts of serum IgA present (r = 0.0507). Moreover, titers of total antibody to MAP related equally well to enzyme-linked immunosorbent assay indicated amounts of IgG antibody (r = 0.3939) and IgA antibody (r = 0.3054) to MAP in rheumatic fever patients but not in nephritis patients (r = 0.0301 for IgA antibody and 0.6909 for IgG antibody to MAP), whereas they related best to IgM antibody to MAP in the school-children (r = 0.4204).

The families of patients with acute rheumatic fever or glomerulonephritis in Trinidad.

The families of 21 patients with acute rheumatic fever (ARF) and 44 patients with acute glomerulonephritis (AGN) in Trinidad were examined in their homes. The ARF and AGN families were equally large and crowded and they lived in the same largely rural areas. However, only 22% of the ARF family members had skin infections in contrast to 61% of the AGN family members. Sixty-eight per cent of skin infections in ARF families and 69% of skin infections in Agn families yielded group A streptococci. Throat cultures were positive in 19% of ARF family members and 25% of AGN family members. Thirty-two per cent of 51 group A strains isolated from ARF family members (29 from throat, 22 from skin) were M11 or "M41" strains which were associated with ARF during the study, while only 8% were M1, T4 (MNT or 60) or M55 strains which were associated with AGN. In contrast, 49% of 171 group A strains isolated from Agn family members (64 from throat, 107 from skin) were M1, T4 (MNT or 60) or M55 while only 10% were M11 or "M41." Serum antibody titers were similar in both groups: antistreptolysin-0 titers were not markedly increased in either while anti-hyaluronidase and/or antideoxyribonuclease-B titers were increased in both. Evidence of subclinical AGN was found equally often in both groups: 6% of each had abnormal urine and 4% of each had decreased serum complement while 2% of the ARF and 3% of the AGN family members had both abnormal urine and decreased serum complement.

Salivary immunoglobulins and streptococcal antibodies in patients with acute rheumatic fever.

Evidence of a local immunologic response to recent pharyngeal infection with group A streptococci was sought in 23 patients with acute rheumatic fever. Salivas from these patients were examined and compared with salivas from control subjects. As assayed, both IgG and IgA values ranged between 8 and 170 mg. per 100 ml. in 10-fold concentrated samples of saliva. When these values were corrected for the concentration of the samples and for the use of serum IgA standards, the following mean values were obtained: for patients with acute rheumatic fever, IgG was 4.5 mg. per 100 ml. and IgA was 8.7 mg. per 100 ml.; for control subjects, IgG was 5.0 mg per 100 ml. and IgA was 9.9 mg. per 100 ml. IgM was present in amounts of 1 to 2 mg. per 100 ml. in 2 patients and 7 control subjects. Antistreptolysin O titers correlated with amounts of IgG in the saliva samples while antihyaluronidase, antigroup A carbohydrate, and antiteichoic acid titers did not. None of the antibody titers correlated with the IgA content of the saliva samples. Furthermore, saliva antibody titers did not differ between patients with acute rheumatic fever and control subjects.

Tropical acute rheumatic fever and associated streptococcal infections compared with concurrent acute glomerulonephritis.

Ninety-three patients with acute rheumatic fever and 195 patients with acute glomerulonephritis were observed in Trinidad during an outbreak of scabies with a high incidence of secondary streptococcal infections. Clinical and laboratory manifestations of ARF were the same as those seen in temperate zones, except that antistreptolysin O titers were less markedly increased. The patients with ARF were similar to those with AGN in respect to sex, race, location of residence, and living conditions, but were older and had markedly fewer skin infections. Currently prevalent nephritogenic streptococcal strains never were isolated from patients with ARF even when M55 streptococci appeared and led to an epidemic of AGN.

Skin infections and immunoglobulin A in serum, sweat, and saliva of patients recovered from poststreptococcal acute glomerulonephritis or acute rheumatic fever and their siblings.

Differences in hygienic habits and base-line secretory immunoglobulin (Ig) A which might have contributed to the prevalence of skin infections and/or absence of increased serum IgA values were sought in patients with poststreptococcal acute glomerulonephritis (nephritis) in contrast to patients with acute rheumatic fever in Trinidad by studying patients and their siblings after the patients had recovered from these diseases. The overall history of skin infections was similar at this time in all groups, although they had been much more common in patients with nephritis and their families at the time of acute illness. The recovered nephritis patients bathed slightly less often than the other individuals, used a cream or lotion after bathing rather than coconut oil, and tended to sweat less than the others, but none of these differences was statistically significant. Neither were significant differences demonstrated in amounts of IgA and IgG in serum and saliva of recovered nephritis patients and their siblings compared to recovered rheumatic fever patients and their siblings, while only small amounts of IgA and IgG were present in any sweat, and probably had been transuded rather than secreted. These studies suggest that the lower serum IgA titers in patients with nephritis compared to patients with rheumatic fever in Trinidad do not reflect basic differences in serum IgA or secretory IgA as measured in saliva, and that IgA is not secreted by the eccrine glands.

Clinical healing two to six years after poststreptococcal glomerulonephritis in Trinidad.

To determine the incidence of chronic nephritis after poststreptococcal acute glomerulonephritis in Trinidad, 760 patients (41 adult) were examined two to six years after recovery from the illness, 344 being studied twice (four and six years). Only 1.8 per cent had persistent urine abnormalities on their last follow-up examination, and another 8.0 per cent had abnormalities that were transient or occurred only after the patient had assumed the lordotic position. In 1.4 per cent hypertension was present, whereas only one had azotemia. Both persistent urine abnormalities and hypertension increased in prevalence with age at onset of prior poststreptococcal glomerulonephritis but did not vary between sexes, races or epidemic versus endemic forms. Half the urine abnormalities present four years after recovery were absent two years later. Thus, poststreptococcal acute glomerulonephritis appears to have a low incidence of chronicity in Trinidad, with continuing resolution for more than four years.