THE SERUM ANTISTREPTOLYSIN TITER INACUTE GLOMERULONEPHRITIS

John D. Lyttle, … , Emily Nichols Loeb, Elizabeth L. Jost

J Clin Invest. 1938;17(5):631-639. https://doi.org/10.1172/JCI100989.

Research Article

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THE SERUMANTISTREPTOLYSIN TITER IN ACUTEGLOMERULONEPHRITIS

By JOHN D. LYTTLE, DAVID SEEGAL, EMILY NICHOLS LOEB,AND ELIZABETH L. JOST

(From the Departments of Medicine and Pediatrics, College of Physicians and Surgeons,Columbia University, the Babies Hospital, the Presbyterian Hospital, and the Research

Division for Chronic Diseases, Department of Hospitals, New York City)

(Received for publication April 28, 1938)

This work on the level of an'tistreptolysin titerin the serum of patients with acute glomerulone-phritis is part of a study being conducted by theDepartments of Medicine and Pediatrics on therole of infection in acute and chronic glomerulo-nephritis. The literature and texts list the mostheterogeneous types of infection (influenza, diph-theria, measles, the common cold, sore throat, ex-posure, osteomyelitis, "pregnancy," intestinal ca-tarrh, pyodermia, etc.), as the prodromal episodein acute glomerulonephritis. For this reason andbecause at the time the patients are first observed(at the onset of the nephritis) the clinical andbacteriological evidence of the preceding infectionmay be inadequate, it seemed desirable to obtainmore specific evidence on the character of theinfection which precedes the nephritis. A pre-liminary study (1) in 1933 showed that of 22patients with acute glomerulonephritis the seraof 20 had a definite increase in antistreptolysintiter. The present report is a more completestudy of this antibody in a larger group of pa-tients observed over a period of four years.

In 1932, Todd (2) demonstrated that the seraof- animals immunized with the hemolysin of theStreptococcus hemolyticus developed a significantamount of an antibody inhibiting the activity ofthis hemolysin. This antibody had been calledantistreptohemolysin or antistreptolysin. Thesera of animals immunized to a variety of otherbacterial antigens did not contain appreciablequantities of this antibody. Later Todd (2),Coburn and Pauli (3), Griffiths (4), Myers andKeefer (5), Lippard and Johnson (6), Wilson,Wheeler, and Leask (7), Blair and Hallman (8),Longcope (9) and others have investigated andreported the antistreptolysin content of the serain normal individuals and in patients with infec-tions resulting from Streptococcus hemolyticusand other organisms.

A description of the technique used in deter-mining the serum antistreptolysin is found in theAppendix of Todd's publication (2). The prep-aration of the medium now used to produce thestreptolysin is that outlined by Todd and Hewitt(10), with the exception that beef heart is usedinstead of horse meat. In the titration of thestreptolysin', however, we follow the method ofHodge and Swift (11) and determine its com-bining unit. For this method we use Dr. Todd'sstandard antistreptolysin horse globulin which hekindly furnished us. In the routine test thisglobulin (diluted so that 1.0 cc.=20,000 units)and normal human sera are run regularly as con-trols.

The normal antistreptolysin titerThere is general agreement that the antistrep-

tolysin level in individuals who have been free ofhemolytic streptococcus infection is less than 100units. Coburn and Pauli (3) found that of 146normal individuals, 75 per cent had a titer of 100units or less; 20 per cent had between 100 and200 units; and 5 per cent had 200 units or more.Longcope (9) found that of 55 normal individualsthe titer was between 25 and 50 units in 75 percent and was above 100 units in only 1 individual.Although Wilson, Wheeler, and Leask (7) con-clude that " a rise in antistreptolysin titer of theserum is not conclusive evidence of streptococcalrespiratory infection," among other workers thereis gen'eral agreement that following infectionswith hemolytic streptococcus, the antistreptolysintiter rises and that high titers may be maintainedfor some time after the infection has subsided.The rise in titer may be moderate in degree andof brief duration, and may be shown only whendeterminations are made for a period before andafter an infection in order to obtain the natural orbasal level. In other words, the antistreptolysin

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J. D. LYTTLE, D. SEEGAL, E. N. LOEB ANDE. L. JOST

titer of an individual taken at random may bedifficult to interpret, but if serial studies are made,interpretation is more accurate and the significanceof moderate elevation of titer is clearer. For ourpurpose we have considered an antistreptolysintiter of 125 units or more as an evidence of recentinfection with hemolytic streptococcus if previousor subsequent determinations show the level tobe lower.

Clinical and bacteriological dataThis report is based on a study of 116 con-

secutive and unselected cases of acute glomerulo-nephritis seen at the Babies Hospital and Presby-terian Hospital from March 1933 through May1937. The diagnosis of acute glomerulonephritisin our patients was based on the presence of thecommonly accepted clinical and laboratory find-ings for this disease. Patients with acute pyelo-nephritis, subacute bacterial endocarditis, or ob-scure forms of acute nephritis are not included.On the clinical side, certain points should be madeclear. There are 95 children under 13 years ofage and 21 adults in our series. Although acutenephritis is more common in childhood, if onestudies the condition only in children or only inadults one does not get a complete picture of thedisease. Our series embraces the characteristicage distribution in acute nephritis. Males pre-dominate 2 to 1 in the series. It is quite probablethat in the majority of attacks of acute nephritisthe disease is so mild that the physician is notconsulted. Many of our patients were admittedto the hospital because of the severity of aninfection and subsequently routine examinationshowed the presence of nephritis. The fact thatwe have been dealing either with the more severeforms of nephritis or with the mild type of ne-phritis occurring in severe infections must beconsidered in interpreting the data. The majorityof patients showed definite clinical and bacterio-logical evidence of hemolytic streptococcal infec-tion but many gave only a vague or negativehistory of preceding infection. It must be re-membered also that even if the patient is ob-served at the onset of the nephritis the infectionis believed to have preceded the nephritis by from10 to 30 days and the direct evidence for thisinfection may be inadequate at the time the patientis first observed.

The great majority of the patients in this serieshad a history or showed evidence of infection ofthe upper respiratory tract preceding or accom-panying the onset of acute nephritis. In 104cases where data were adequte, the infection waslocated in the upper respiratory tract or its ap-pendages. In 12 of the 116 cases the data wereinsufficient to make a clinical diagnosis. The clin-ical diagnoses are shown in Table I.

TABLE I

Clinical diagnosesCommoncold ............................ 8Sore throat ............................. 14Sinusitis ............................. 1Cervical lymphadenitis .................... 11Peritonsillar abscess and cervical abscess... . 15Otitis media ............................. 8Mastoiditis ............................. 29Scarlet fever ............................. 11Measles ............................. 2Pneumonia ............................. 3Peritonitis ............................. 2

104

In 6 of these 104 cases no cultures were made.In 46 patients with upper respiratory infection,throat cultures were negative for hemolytic strep-tococcus in 18 and positive in 28. The possibilityof an antecedent hemolytic streptococcal infectionin the patients showing negative cultures on ad-mission is not excluded since cultures were takenanywhere from 2 to 6 weeks after the onset ofinfection. In 7 of the 18 patients with negativethroat cultures a culture taken from the excisedtonsils during convalescence showed hemolyticstreptococcus. Of 51 patients with an activefocus of infection (peritonsillar abscess, mastoi-ditis, etc.), 47 had a positive culture for hemo-lytic streptococcus. The 2 patients with measlesand 2 of the 3 patients with pneumonia had posi-tive throat cultures for hemolytic streptococcus.In summary, 83 or 71.5 per cent of the 116 caseshad bacteriological evidence of infection withhemolytic streptococcus while 33 or 28.5 per centhad negative bacteriological evidence of hemolyticstreptococcal infection.

Though all patients that were observed in theacute stages are included for a general survey,we have selected for more careful analysis groupsof cases who were seen early in the course of thedisease and who were followed through to com-plete healing or to the development of chronic

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ANTISTREPTOLYSIN IN NEPHRITIS

glomerulonephritis. In these groups more com-plete clinical and immunological data make pos-sible an attempt to discover any correlation be-tween the immunological data and the clinicalcourse.

The maximum antistreptalysin titer during theacute stage of glomerulonephritis

Figure 1 presents the maximum titer of anti-streptolysin found in 116 consecutive cases of

40b* 40-

0S

o20-

1-z

10 144 200 500 1000 2000I I I I I I

125 166 333 833 1666 2500

ANTISTREPTOLYSIN TITER IN UNITSFIG. 1. MAXIMuMANsmwEPIroLYsIN TITER IN 116

CASES OF AcuTE GLOMERULONEPHRInIS

acute glomerulonephritis. The maximum titer isusually reached in the first few weeks of the dis-ease, which has its onset about 2 weeks followingthe acute infection. The highest antistreptolysintiter in the first 40 days after the onset of thenfephritis is shown in each case. It is apparentthat in 94 per cent of 116 cases the antistreptolysintiter was above 125 units and in 27 per cent thetiters were between 1000 and 2500 units. Sincewe consider 125 units to be the upper normallevel of antistreptolysin, this lends further sup-port to the results of direct culture just quotedand indicates that the great majority of patientswith acute glomerulonephritis have had a recenthemolytic streptococcal infection.

There were 7 patients (5 children, 2 adults)whose maximum antistreptolysin titer was 125units or less. In 2 children determinations werenot made until the 35th and 38th day of thenephritis and corresponidingly later after the acuteinfection. Hence the rise so commonly observed

in the first weeks of the disease may have beenmissed in these cases. In both these patients themaximum antistreptolysin was 125 units and sub-sequent determinations after the nephritis hadhealed showed the basal level to be between 55and 62 units in one patient and 20 and 33 unitsin the other. These later observations suggestthat the 125 unit level represented a significantintcrease in antistreptolysin titer for both patients.In another child who had a history of sore throatand cervical lymphadenitis preceding the nephritis,titers were determined frequently from the 8thday after the onset of the nephritis, yet the high-est antistreptolysin titer found was 125 units.There was no bacteriological evidence of hemo-lytic streptococcal infection but min'imal urinarychanges persisted for one year, and for 15 monthsafter onset the antistreptolysin titer remained at100 to 125 units. It was of interest, however,that at 2 years and at 3 years after the onset ofthe nephritis the antistreptolysin titers were 72and 71 units. In the fourth patient a mild acutenephritis followed an operation for ruptured ap-pendix and peritonitis. Colon bacilli and hemo-lytic streptococci were cultured from the peri-toneal fluid at operation, yet four antistreptolysindeterminations during the acute stages of thenephritis showed values of less than 10 units.We have no explanation for the failure of theantistreptolysin titer to rise in this patient. Ina fifth instance a 12-year-old boy gave a historyof a sore throat followed in 11 days by hematuriaand edema and accompanied by a recrudescenceof the sore throat and cervical lymphadenltis.He was first observed on the 8th day after theonset of the nephritis. At this time, throat cul-ture showed pneumococci predominating, and theantistreptolysin titer was 100 units. On the 22dday the antistreptolysin titer was 83 units. Sevenantistreptolysin determinations made in the next2 months showed titers of 62 or 71 units. Bac-teriologically, no hemolytic streptococcal infec-tion was ever proven to exist in this patient. Onecan postulate that the initial titer of 100 units isa rise over the subsequent basal level and mayrepresent the patient's response to hemolyticstreptococcal infection. It is also possible thathemolytic streptococcal infection had nothing todo with this case of nephritis.

In the adult group two patients failed to show

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J. D. LYTTLE, D. SEEGAL, E. N. LOEB AND E. L. JOST

any rise in antistreptolysin titer. Case G. R., a38-year-old female, developed acute glomerulo-nephritis 21 days following lobar pneumon'ia re-sulting from Pneumococcus Type III. At notime was there clinical or bacteriological evidenceof hemolytic streptococcal infection. Repeatedantistreptolysin determinations during the acutestage and for 15 months after the onset of thenfephritis showed titers of 35, 55, and 62 units.The nephritis here may have resulted from apneumococcal infection. The second adult, J. W.,31-year-old male, had a sore throat followed in8 days by smoky urine, edema, and hypertension.He was first observed on the 10th day after onsetof nephritis when the antistreptolysin titer was83 units. At this time, throat cultures were nega-tive for hemolytic streptococcus and there wasno evidence of any other focus of infection. Hedeveloped chronic glomerulonephritis, and 11 anti-streptolysin titers in the course of the first yearwere 100 or 111 units. No hemolytic streptococ-cal infection was proven in this patient and nosignificant rise in antistreptolysin titer was ob-served.

Maximum antistreptolysin titer and sex. Ourfigures fail to show any significant differencesbetween the sexes in their ability to develop anti-streptolysin in response to hemolytic streptococcalinfection.

Maximum antistreptolysin titer and age. Sincethe adult group is small in relation to the numberof children, it is difficult to say whether certainapparent correlations of antistreptolysin level withage are significant. Of 21 adult cases, 5 hadmaximum titers of 166 or less, whereas only 6 of95 children had maximum titers of 166 or less.Of 13 children under 2 years of age, 8 developedmaximum titers of 500 units or higher. This isnot in agreement with the experience of Lippardand Johnson (6) who found that the majority ofyoung infants who recovered from hemolyticstreptococcal infection without developing nephri-tis did not show striking increases in antistrep-tolysin titer.

Maximum antistreptolysin titer and infection.The most striking correlation between the maxi-mumantistreptolysin titer and the various clinicalfeatures exhibited by the patients in this serieswas that in relation to the severity of the preced-ing infection. It has been previously stated that

only one type of infection has been described foreach patient. For instance, if a patient wasshown to have had an acute pharyngitis, otitismedia, and mastoiditis, the most severe of theseconditions was the one used to describe the pro-dromal infection for that patient. Table II illus-trates the relationship between the maximum anti-streptolysin and the type of infection.

TABLE II

Relaion of maximum antistreptolysin titer andtype of infection

TpeofcUnits of antistreptolysin Num-Iction of

10-125 144-166 200-333 500-833 1000-2500 ces

Peritonsil-larabscess 0 1 4 3 1 9Scarletfever ..... 0 0 6 2 2 10Pharyngi-tis, tonsil-litisl . ....1 0 7 9 1 18Cervicallymphade-nitis ..... 0 1 7 8 6 22Otitismedia,mastoiditis 0 1 7 8 21 37

Numberof cases. . 1 3 31 30 31 96

In the group with low titers, the diagnosisotitis media, cervical lymphadenitis, and peri-tonsillar abscess occurs only once. In the groupwith a moderate elevation of the antistreptolysinvalue, the cases of otitis media and mastoid dis-ease, cervical lymphadenitis and scarlet fever areequally divided. In the group with titers of 500to 833 units, otitis media and mastoiditis, cervicallymphadenitis and peritonsillar abscess accountfor two-thirds of the cases; but in the group withhigh titers (1000 to 2500 units) these diagnosesaccount for 90 per cent of the cases. It shouldbe noted that these infections are frequently cu-mulative, that is, a patient with mastoiditis may beassumed to have had a pharyngitis and cervicallymphadenitis before the otitis media and mastoi-ditis developed.

Maximum antistreptolysin titer and degree ofinfection and dcgree of nephritis. An attemptwas made to correlate the severity of the infec-tion and the severity of the nephritis with themaximum antistreptolysin titer in 101 patients.

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ANTISTREPTOLYSIN IN NEPHRITIS

Estimates as to the severity of infection' and ofnephritis are of necessity only gross. Uncom-plicated scarlet fever, pharyngitis, and a transientcervical lymphadenitis were regarded as mild in-fections. Peritonsillar abscess, cervical lymph-adenitis which progressed to abscess formationand mastoiditis were looked upon as severe infec-tions. The severity of the nephritis was gaugedby the degree and duration of the urinary changes,hypertension, edema, and nitrogen retention.Table III shows the data in this regard.

TABLE IU

Maximum antistreptolysin titer in 101 patients in rektion toseversty of infection and nephritis

Units of antistreptolysin Num______- - - - ____ ____ ber

Severity of infection of10- 144- 200- 500- 1000- 2000- caes125 166 333 833 1666 2500

Group iSevere infectionwith mild nephritis 1 2 12 11 22 3 51

Group 2Severe infectionwith severe neph-ritis ........... 0 1 3 4 4 0 12

Group 3Mild infectionwith mild nephritis 2 0 6 8 1 0 17

Group 4Mild infectionwith severe neph-ritis........2 1 9 7 2 0 21

101

In the first group are tabulated the results inthose patients with a severe infection and a mildn'ephritis. Half of the 101 patients are found tobe in this group. The antistreptolysin titer was

elevated in all but one patient, with only slightelevation in two patients. From what has beensaid one would expect to find the largest numberof high titers in this group, and this is so. Ofthe 51 patients, 50 per cent showed maximuman'tistreptolysin titers over 1000 units and 70 per

cent exhibited values over 500 units. It is ofinterest that none of the patients in this group

developed chronic nephritis.In Group 2 are tabulated the figures from 12

patients with a severe infection and a severe ne-

phritis. The results are similar to those in thefirst group, over half having titers of 500 units

or higher. But in this group are 3 of the 8 pa-tients who developed chronic nephritis. One ofthese patients had mastoiditis and two had a peri-tonsillar abscess, infections which usually give avery high antistreptolysin titer, yet in these pa-tients the titers were 250, 144, and 833 unitsrespectively. However, it cannot be said that thefailure to develop a high titer following a severein'fection points to the probability of the subse-quent development of chronic nephritis, for it isseen in Group 1 that 15 patients with severe in-fections did not reach high levels yet the nephritishealed promptly.

In Group 3 are the antistreptolysin values of17 patients with mild infection and mild nephritis.The nephritis healed promptly in all cases. Inall but two patients the antistreptolysin titers wereabove normal. In Group 4 are the figures for21 patients with mild infection and severe ne-phritis including 5 patients who developed chronicnephritis. The distribution of maximum anti-streptolysin titers is practically identical in thesetwo groups.

From the data presented, it appears that severenephritis is not usually accompanied by extremelyhigh antistreptolysin titers. Of 32 patients withantistreptolysin titers of 1000 units or higher only6 or 18.7 per cen't had severe nephritis and nonedeveloped chronic nephritis.

Maximum antistreptolysin titer and duration ofnephritis. Healing occurred in 108 of the 116cases within 1 year. No correlation could be es-

tablished between the maximum antistreptolysinresponse and the rapidity with which healing oc-

curred or the development of chronic nephritis.Of the 8 patients who progressed to chronic ne-

phritis 5 had a mild infection, with normal anti-streptolysin titers in 2 and moderate elevation(144, 200, 714 units) in 3 patients. Three hada severe infection with only moderate elevationof antistreptolysin titer in 2 (144, 250 units) anda rise to 833 units in one patient. It is obviousthat the number of patients who developed chronicnephritis under observation is too small to war-ran't conclusions, but the data available suggestthat low antistreptolysin titers in acute nephritisdo not indicate that chronic nephritis will developor that the development of chronic nephritis isalways associated with low antistreptolysin titers.

635

J. D. LYTTLE, D. SEEGAL, E. N. LOEB AND E. L. JOST

COMMENT

Longcope (9) studied 36 adult patients duringthe acute stage of hemorrhagic nephritis.Twenty-three patients or 64 per cent showed anti-streptolysin titers above 125 units. The highesttiter observed was 500 units, found in 2 patients.The type of infection accompanying the nephritiswas quite different in Longcope's series from ours.The deep infections such as mastoiditis and cer-vical lymphaden'itis which occurred so frequentlyin our series where children predominate are notfound in the group observed in Baltimore. Thismay account for the smaller percentage of casesshowing antistreptolysin elevation and the lack ofvery high antistreptolysin titers.

Careful study of our clinical and immunologicaldata indicate that in the acute stages of glomerulo-nephritis the maximum antistreptolysin titer is(1) not related to age or sex, (2) has no relationto the severity or duration of the nephritis, but(3) is definitely related to the type and severityof the acute infection which precedes or accom-panies the acute nephritis.

The data presen'ted here establish the fact thatin spite of the heterogeneous group of prodromalinfections observed or the unsatisfactory historyand clinical evidence of the preceding infectionin many cases, 94 per cent of 116 consecutivecases of acute glomerulonephritis show specificimmunological evidence of havin'g had a recenthemolytic streptococcal infection.

The titer of antistreptolysin following acuteglomerulonephritis

The diagram in Figure 2 shows the variationsin immune response during the two years fol-lowing the onset of acute nephritis. This dia-gram was made by using only the highest anti-streptolysin titer found for each patient in eachof the first twelve months after onset. For thesecond year after the onset, all the antistreptolysindeterminations on each patient studied are in-cluded. The majority of the 63 patients in thisgroup had from 4 to 8 antistreptolysin determina-tions during this 2-year period.

The diagram shows that in the second monththe number of normal titers begins to increaseand the number of high titers decreases. In thesecond year after onset the titers in 75 per cent

PERCENT0 20 40 6* SO 190.I I I I I

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11 zC

91 aa

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97 to

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_125 1466 200_333 50!33 OO2Soo

FIG. 2. TiTER OF ANTISTREPTOLYSIN FOLLOWINGACUTEGLOMERULONEPHRITIS

of the patients are niormal and 25 per cent havetiters from 144 to 333 units. At this time thenephritis had healed in all but 8 patients. Thisperiod serves as a control for the group and thesefigures are in good agreement with the controlgroup of Coburn and Pauli in New York Citywho found that 75 per cent of 146 individualshad titers of 100 units or below.

In Figure 3 are presented curves to show thevariations in antistreptolysin titer in the first yearafter the onset of nephritis. In 71 patients de-terminations were made frequently enough sothat a significant curve could be made. Thesecurves fall roughly into 7 groups; two curves areshown as representative of each group.

Group A. Thirteen of the 71 patients showedthis type of response. Five of the 8 patients whodeveloped chronic nephritis were in this group.The significance of this will be discussed later.

Group B. Thirteen patients showed this typeof curve, i.e., a moderate initial rise and a promptfall to normal levels. All except one individualrecovered completely.

Group C. Ten patients showed this type ofcurve, an initial rise to 500 units with a tendencyto moderate elevation of titer at the end of thefirst year. All these patients recovered.

Group D. Twelve patients showed this type ofresponse, a high initial rise (800 units) with nor-mal titers by the third month. Two patients who

636

ANTISTREPTOLYSIN IN NEPHRITIS

4C 2000.) 600 1800

4001600P

200 1200.

*4

'tfothI

400 . 800

200W ~600

________________ _____ 400.

200A2.I1Z34 56 7 891011 12 12'3

Month5FIG. 3. VARIATIONS iN ANTISTREPMrLYSIN T:

developed chronic nephritis showed this type ofresponse.

Group E. Three patients showed extremelyhigh initial titers with a slow fall toward normallevels but at the end of the first year the titerswere still abnormally high.

Group F. Thirteen patients showed extremelyhigh initial titers with normal titers after the 6thmonth. All recovered.

Group G. Seven patients showed either a ris-ing titer in convalescence or a secondary rise afterthe initial rise and fall in titers. In all these pa-tients there was an exacerbation of the infectionor a reinfection by hemolytic streptococcus.

DISCUSSION

The great majority of individuals who havehemolytic streptococcal infection followed by anattack of acute glomerulonephritis develop a sig-

Month5 MonthsITER IN THE FIRST YEAR OF AcuTE NEPHRITIS.

nificant rise in antistreptolysin titer. But thisresponse is known to occur in individuals in whomhemolytic streptococcal infection is not followedby acute glomerulonephritis.

The maximum antistreptolysin titer is presentat the onset or during the first few weeks of theattack of acute nephritis but the significance ofthis fact is not apparent. The maximum rise inantistreptolysin titer may be of all degrees andthe clinical findings in the patients who developedextremely high antistreptolysin titers are not dif-ferent from those who developed a moderate orintermediate rise in antistreptolysin titer.

The fact that 5 of the 8 patients who developedchronic nephritis showed only moderate elevationof antistreptolysin titer (Group A, Figure 3) isinteresting.

The value of x2 calculated from Table IV us-ing Yates' correction is 8.676. The value re-

637

J. D. LYTTLE, D. SEEGAL, E. N. LOEB AND E. L. JOST

TABLE IV

Relation of antistreptolysin titer and the development ofchronic nephritis

Moderate elevation Intermediate andof antistreptolysin high elevation of Total

titer antistreptolysin titer

Chronicnephritis. . 5 3 8

Healednephritis. . 8 55 63

Total....... 13 58 71

quired to demonstrate significant (P = 0.01) de-viation from random sampling 6.635. Whilethese figures are statistically significant there are

too many other factors to be considered in theevolution of chronic glomerulonephritis and thenumber of cases is too small to make possible a

definite conclusion. Further study may throwmore light on this point.

In the majority of patients the antistreptolysintiter begins to fall in the first or second monthof the disease and in half the patients the anti-streptolysin titer is normal by the 6th month.In this period the nephritis begins to improveclinically as measured by the disappearance ofhypertension and edema, diminution in albumin-uria and hematuria, and by the return of normalkidney function. But this finding may be co-

incidental rather than correlative since analysisof the data accumulated in the 2-year period afterthe onset of the nephritis shows no correlationbetween the rate at which the antistreptolysin titerreturns to normal and the clinical changes in thepatient. *In the second year after the onset ofthe nephritis when 108 of the 116 patients were

healed, the antistreptolysin titer was normal in75 per cent with 25 per cent of the patients show-ing a moderate elevation (144 to 333 units).

It is well known that antibody responses tovarious infections may persist for a long timeafter the acute infection has subsided. That thisis true also of antistreptolysin is shown in thecharts. Recently Todd expressed the opinionbased on animal work that the persistence of highantistreptolysin titers in convalescence signifiespersistence of the infection. A study of our

cases indicates that this is probably true in hemo-lytic streptococcal infection in man. In all 31of our patients in whom high titers either per-sisted or recurred after the initial rise and fall

there was definite clinical or bacteriological evi-dence of the persistence or recurrence of infection.These patients were carefully studied for informa-tion as to the effect on the nephritis of the per-sistent or recurrent infection. In only 10 of the31 patients could it be said that the infection hadan adverse effect on the nephritis. This effectwas shown in some cases by an increase in hema-turia and albuminuria and in others by the per-sistence of well-marked hematuria and albumin-uria. It is believed by some workers thatpersistence of the infection or the recurrence ofinfection in convalescence from nephritis is as-sociated with persistence or exacerbation of thenephritis. This may be true in some cases butit is certainly not the rule. Longcope states thatwhen " the disease progressed to a chronic stagethe antistreptolysin titer remained at a high levelin a fair proportion of instances." The role ofhemolytic streptococcal infection on the courseof chronic nephritis is to be considered elsewhere(12) but it can be said here that, in this series, inthe 8 patients who progressed to chronic nephritisthe level of antistreptolysin was normal in all at6 months and has remained normal during thesubsequent period of observation.

CONCLUSIONS

1. In 116 consecutive cases of acute glomeru-lonephritis the bacteriological data indicate that71.5 per cent had a prodromal hemolytic strep-tococcal infection, and the immunological datashow that 94 per cent had had a recent hemolyticstreptococcal infection.

2. The height and duration of the antistrep-tolysin titer in patients with acute glomerulone-phritis appear to be related to the severity,persistence, or recurrence of the hemolytic strepto-coccal infection.

3. Analysis of the immunological and clinicaldata in the present study does not show anysignificant correlation between the height andduration of the antistreptolysin response and theseverity or duration of the acute attack of nephri-tis or the tendency to develop chronic nephritis.

4. There is a wide variation in the curve ofantistreptolysin response constructed over a longperiod of time. The form of the curves has norelation to the severity or duration of acute ne-

638

ANTISTREPTOLYSIN IN NEPHRITIS

phritis or to the tendency to develop chronicnephritis.

BIBLIOGRAPHY1. Seegal, D., and Lyttle, John D., Antistreptolysin titre

of the serum in acute glomerular nephritis. Proc.Soc. Exper. Biol. and Med., 1933, 31, 211.

2. Todd, E. W., Antigenic streptococcal hemolysin. J.Exper. Med., 1932, 55, 267.

Todd, E. W., Antihaemolysin titres in haemolyticstreptococcal infections and their significance inrheumatic fever. Brit. J. Exper. Path., 1932, 13,248.

3. Coburn, A. F., and Pauli, Ruth H., Studies on theimmune response of the rheumatic subject and itsrelationship to activity of the rheumatic process.VI. The significance of the rise of antistreptolysinlevel in the development of rheumatic activity.J. Clin. Invest., 1935, 14, 769.

4. Griffiths, G. J., Antihaemolysin titres in chronicrheumatic and allied diseases. Lancet, 1934, 2,251.

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