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Infection in patients with systemic lupus erythematosus.

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1326
INFECTION IN PATIENTS WITH
SYSTEMIC LUPUS ERYTHEMATOSUS
Association with a Serum Inhibitor of Complement-Derived Chemotactic Activity
H. DANIEL PEREZ, RICHARD I. ANDRON, and IRA M. GOLDSTEIN
We have found subnormal amounts of chemotactic activity in zymosan-treated sera from 13 of 29
patients with systemic lupus erythematosus (SLE). As
an explanation for this abnormality, the presence of a
uniquely specific, heat-stable inhibitor of complement
(C5)derived chemotactic activity has been documented
in sera from 11 of these patients. Sera from 2 other patients contained elevated levels of nonspecific, heat-labile chemotactic factor inactivator (CFI) activity. The
serum from 1 patient contained the heat-stable inhibitor
as well as elevated levels of CFI. Patients with SLE
whose sera contained the heat-stable inhibitor had more
active disease clinically, but otherwise they were indistinguishable from patients without the inhibitor.
When patients with the heat-stable inhibitor improved
clinically, this usually was accompanied by a decrease in
serum inhibitory activity. Only one episode of bacterial
infection was observed among 16 patients with SLE
whose sera yielded normal amounts of chemotactic activity after treatment with zymosan. In contrast, 7 of 11
patients with SLE whose sera contained the heat-stable
From the Department of Medicine, Division of Rheumatology, New York University Medical Center, New York, NY 10016.
Supported by grants from the National Institutes of Health
(AM-18531, AM-11949, GM-2321 I, and HL-19721). the National
Foundation-March of Dimes, and the National Science Foundation
(76-0562 I).
H. Daniel Perez, MD: Instructor in Medicine, recipient of
NIAMDD Clinical Investigator Award (AM-00463); Richard I.
Andron, MD: Fellow, Division of Rheumatology; Ira M. Goldstein,
MD, FACP Associate Professor of Medicine, recipient of a Career
Scientist Award from the Irma T. Hirschl Trust.
Address reprint requests to H. Daniel Perez, MD,Department of Medicine, New York University Medical Center, 550 First
Avenue, New York, NY 10016.
Submitted for publication March 6, 1979; accepted in revised
form July 14, 1979.
Arthritis and Rheumatism, Vol. 22, No. 12 (December 1979)
inhibitor suffered serious bacterial infections. The presence of this heat-stable inhibitor in sera from some patients with SLE may contribute, in part, to their increased susceptibility to infection.
Patients with systemic lupus erythematosus
(SLE) appear to be particularly susceptible to infections
caused by common pyogenic microorganisms (1-4).
Whereas modem therapy with adrenal corticosteroids is
undoubtedly a contributing factor (3,4), there is some
evidence that the disease per se is associated with abnormalities of host defenses against infection (4- 10).
We have recently reported one such abnormality involving complement-derived chemotactic activity for
polymorphonuclear leukocytes (PMN) (1 1). We found
that sera from 5 of 11 patients with SLE, when activated
with zymosan, failed to attract normal human PMN
comparably to zymosan-activated control serum. Incubation of normal PMN with sera from those patients
did not affect either the random motility of the cells or
their ability to respond to chemoattractants. Serum
from 1 patient, however, did contain elevated levels of a
previously described nonspecific, heat-labile chemotactic factor inactivator (CFI) (12). Sera from the other
4 patients contained a previously unrecognized inhibitor of complement-derived chemotactic activity. The
inhibitor was heat-stable and uniquely specific. It acted
reversibly only on chemotactic peptides derived from
the fifth component of complement (C5). It had no effect on the chemotactic activity exhibited by various
concentrations (all suboptimal) of either the bacterial
chemotactic factor from Escherichiu coli or the chemotactic synthetic peptide, N-formylmethionylleucylphenylalanine. Too few patients were examined to de-
INFECTION IN SLE PATIENTS
termine whether t h e presence of this heat-stable
inhibitor was associated with any specific clinical o r laboratory parameters of disease activity. Consequently,
we have extended our studies and now report findings
in 29 patients with SLE.
MATERIALS AND METHODS
Patient population. Twenty-nine patients with well
documented SLE who were followed by the Rheumatology
Division at New York University Medical Center were studied. The only criteria used to select patients for study were the
availability of samples of blood for laboratory testing and the
absence of severe impairment of renal function (blood urea
nitrogen greater than 35 mg/dl or serum creatinine greater
than 2.0 mg/dl). The criteria for diagnosis of SLE were those
of the American Rheumatism Association (13). The patients
ranged in age from 18 to 56 years (mean 34 years) and all
were women. Duration of disease ranged from 6 months to 23
years (mean 6 years). The extent of disease activity in these
patients was assessed according to the criteria of Rothfield
and Pace (14). Grade 0 was assigned to patients without clinical evidence of disease activity; Grade 1 to patients with disease activity involving one organ system without fever; Grade
2 to patients with active involvement of one system with fever
or involvement of more than one system; and Grade 3 to patients with involvement of at least two systems with fever. Remissions were classified as either partial or complete. Partial
remission was defined as a transition from Grade 2 or Grade 3
disease activity to Grade 1. Complete remission corresponded
to Grade 0.
Eighteen patients with rheumatoid arthritis (RA) were
also studied. All were seropositive and met the criteria for the
diagnosis of classic rheumatoid arthritis established by the
American Rheumatism Association (15). There were 10
women and 8 men in this group, ranging in age from 42 to 65
years (mean 55 years). Duration of disease ranged between 1
and 21 years (mean 8 years). None of these patients had abnormal renal function and none was receiving therapy with
corticosteroids.
Two additional groups of patients were studied. The
first consisted of 17 patients admitted to New York University
Medical Center for treatment of systemic bacterial infections.
All infections were documented by blood cultures and were
similar to those observed in patients with SLE. None of these
patients had clinical or laboratory evidence of either rheumatic or hematologic disease. There were 8 men and 9 women
in this group, ranging in age from 23 to 80 years (mean 52
years). The second group included 21 healthy volunteers, 18
women and 3 men, ranging in age from 20 to 40 years (mean
29 years).
Preparation of leukocyte suspensions and sera. Human PMN were isolated from venous blood by dextran sedimentation, as described previously (1 1). Cell pellets were
washed once with isotonic saline and finally suspended in 10
mM phosphate-buffered saline (Grand Island Biological Co.,
Grand Island, New York) supplemented with 0.6 mM CaCl,,
1.0 mM MgCl,, and 2% (wt/vol) bovine serum albumin. This
buffer was adjusted to pH 7.4 and was used throughout. Cell
I327
suspensions contained approximately 85% PMN. Sera were
obtained from clotted blood after centrifugation and either
.
used fresh or stored in aliquots at -7OOC.
Chemotactic factors. Chemotactic activity was generated in sera by adding zymosan (1.O mg/ml, ICN Nutritional
Biochemicals Division, International Chemical and Nuclear
Corp., Cleveland, Ohio) (1 1). After 15 minutes of incubation
at 37OC, the zymosan-sera suspension was centrifuged at
3000g for 10 minutes, and the particle-free supernate was used
directly (diluted with buffer as indicated for each experiment).
Chemotactic activity in zymosan-treated sera is attributable
primarily to C5-derived peptides (16). Partially purified C5derived chemotactic peptides were isolated as previously described (1 1) by molecular sieve chromatography of zymosanactivated normal sera.
Other chemoattractants included the synthetic peptide, N-Formylmethionylleucylphenylalanine (N-formyl-metleu-phe; Peninsula Laboratories, Inc., San Carlos, California)
(17) and a bacterial chemotactic factor from E coli. The latter
was prepared according to the method described by Ward et
a1 (18).
PMN chemotaxis. PMN random motility and directed
migration (chemotaxis) were assessed as desctibed previously
(1 1) by employing the “leading front” method of Zigmond
and Hirsch (19). Modified Boyden chambers containing cells
and chemoattractants were incubated at 37°C for 45 minutes
in an atmosphere of 5% C02 and 100% humidity. The response of PMN either to buffer alone (random motility) or to
chemotactic stimuli was measured as the distance the leading
front of cells migrated into the filter &m/45 minutes). Triplicate chambers were employed in each experiment, and 10
fields were examined in each filter.
For experiments in which unactivated sera were
added to the lower compartments of the modified Boyden
chambers, concentrations were selected that did not by themselves enhance PMN migration in excess of that observed
when albumin-containingbuffer was employed alone (20).
RESULTS
Chemotactic activity in zymosan-treated SLE
serum. Sera obtained from 29 patients with SLE were
activated with zymosan and examined for the presence
of chemotactic activity. Zymosan-treated sera from 13
patients failed to attract PMN comparably to zymosantreated normal sera (Table 1). Whereas it was possible
that the subnormal amounts of chemotactic activity in
zymosan-treated sera from these 13 patients resulted
from abnormalities involving the complement system,
this possibility was not explored further. We have demonstrated previously (1 1) that decreased chemotactic activity in some zymosan-treated SLE sera could not be
attributed either to modestly depressed levels of serum
complement or to failure of zymosan to activate the alternative complement pathway. Consequently, all sera
were examined for the presence of heat-stable inhibitory activity directed specifically toward CS-derived
PEREZ ET AL
1328
Table 1. Decreased chemotactic activity in zymosan-treated SLE
serum
Stimulus
PMN migration m / 4 5 min)*
Buffer alone (random motility)
Zymosan-treated normal sera?
Zymosan-treated SLE sera:?
DS
LM
PG
RJ
LN
JH
EL
AJ
MC
99.6 f 2.9
135.9 f 2.2
113.5 f 1.6
112.1 f 3.1
107.3 f 2.7
106.0 2.0
112.4 2.6
114.5 f 2.8
109.7 f 2.3
108.1 f 2.2
109.5 f 2.3
111.1 f 3 . 5
110.2 f 2.0
113.3 f 4.0
123.4 f 3.6
*
*
cs
AT
MR
IV
* Results represent the mean f SEM of three experiments using
polymorphonuclear leukocytes (PMN) from different normal donors.
t Zymosan-treated sera were used at a concentration of 2.0% (vol/
vol).
chemotactic peptides as well as for elevated levels of
heat-labile CFI activity. Fresh and heated (56°C for 30
minutes) sera were incubated with suboptimal concentrations of CS-derived peptides, the bacterial chemotactic factor from E cdi, and the chemotactic synthetic
peptide, N-formyl-met-leu-phe. Heat-stable inhibitory
activity directed specifically toward CS-derived chemotactic peptides was found in sera from 11 patients.
Heated sera from each of these patients inhibited the
chemotactic activity generated in zymosan-treated normal serum (Table 2). Only 3 patients with SLE were
found to have elevated levels of heat-labile CFI activity.
Only unheated sera from these 3 patients inhibited the
chemotactic activity of the bacterial factor and N-formyl-met-leu-phe (Table 3). Serum from 1 of these 3 patients also contained the heat-stable inhibitor. Neither
the heat-stable inhibitor nor elevated levels of CFI activity (not shown) were detected in sera from 18 patients
with RA, 17 non-SLE patients with systemic bacterial
infection, or 2 1 healthy volunteers (Figure 1).
Clinical and laboratory findings in patients with
SLE. The patients with SLE were divided into two
groups based on whether their sera, after activation with
zymosan, contained normal amounts of chemotactic activity (Table 4). Assignment to either group was determined by the results obtained by examining the initial
sample of serum available from eeach patient. Both
groups proved to be comparable in age and duration of
disease. Furthermore, there were no significant differences when erythrocyte sedimentation rates, levels of
C3 and C4 (determined immunochemically) (21), and
therapy with corticosteroids were compared. The two
groups did differ, however, with respect to the clinical
activity of their SLE. Based on the criteria of Rothfield
and Pace (14), the SLE patients with abnormal chemotactic activity in their zymosan-treated sera also tended
Table 2. Effect of normal and SLE sera on C5-derived chemotactic activity
Stimulus
Buffer alone (random motility)
Zymosan-treated normal sera
heated normal serum$
+ heated SLE serum:$
DS
LM
PG
RJ
+
LN
JH
EL
AJ
MC
cs
AT
PMN migration
m / 4 5 min)*
Percent inhibition of
chemotactic activity?
100.1 f 1.3
137.0 f 2.0
136.1 f 3.1
-
116.4 f 1.1
111.1 f 3 . 7
110.8 f 4.0
106.0 f 2.4
116. I f 1.0
117.7 f 1.2
110.5 f 4.0
107.7 f 2.3
113.6 f 1.9
113.9 f 1.3
112.7 f 1.0
66.8%
70.0%
71.0%
83.8%
66.5%
52.2%
72.5%
79.2%
63.3%
62.5%
65.7%
* Results represent the mean f SEM of five experiments in which PMN from different normal donors
was used.
t Net PMN chemotaxis (minus random motility) in the presence of SLE sera/net PMN chemotaxis in
the presence of normal sera X 100.
$ Zymosan-treated sera were preincubated ( I : I, vol/vol) for 30 minutes at 37°C with heated (56OC for
30 minutes) normal or SLE sera. The final concentration of zymosan-treated sera was adjusted to 2.0%
(vol/vol).
1329
INFECTION IN SLE PATIENTS
Table 3. Elevated levels of chemotactic factor inactivator (CFI) activity in sera from three patients with
SLE
~
~~
% inhibition of chemotacticactivity by SLE sera?
Chemotactic stimulus*
Zymosan-treated normal sera (2.055, vol/vol)
+ SLE sera
+ heated SLE sera
Bacterial chemotactic factor (5.0%, vol/vol)
+ SLE sera
+ heated SLE sera
N-formyl-met-leu-phe (1 x lo-%)
+ SLE sera
+ heated SLE sera
MR
IV
EL*
35
None
34
None
63
60$
86
None
35
None
41
None
60
44
80
None
None
None
Chemotactic stimuli were incubated with equal volumes of fresh or heated (56OC for 30 minutes)
SLE sera at 37°C for 30 minutes.
t PMN chemotaxis @/45 min) in the presence of SLE sera/PMN chemotaxis @/45 min) in the
absence of SLE sera X 100.
Patient EL serum contained heat-labile CFI activity as well as the heat-stable inhibitor of CS-derived
chemotactic peptides.
*
to have more active disease clinically. Seven of 13 were
assigned to Grade 3, 4 to Grade 2, and 2 to Grade 1.
Seven of the 11 patients in this group whose sera contained the heat-stable inhibitor had Grade 3 clinical activity. One of the patients with heat-labile CFI activity
100
7
dKuML
SLE
(291
Rheumatoid
Arthritis (181
-
Figure 1. Presence of a heat-stable inhibitor of complement (CS)-derived chemotactic activity in sera from some patients with SLE.
Zymosan-treated normal sera were incubated at 37°C for 30 minutes
with equal volumes of heated (56°C for 30 minutes) SLE, non-SLE,
RA,and normal sera. The final concentration of zymosan-treated sera
was 2.0% (vol/vol). Results are expressed as percent inhibition of the
chemotactic activity observed in zymosan-treated sera alone (see
Table 2).
in the serum was classifled as having Grade 2 clinical
activity, whereas the other 2 were assigned to Grade 1.
In contrast, of the 16 patients with normal chemotactic
activity in their zymosan-treated sera, only 3 fulfilled
the criteria for Grade 3 activity. Twelve of these patients were classified as Grade 2 and l as Grade l. Only
among the group of 11 patients with the heat-stable inhibitor was the incidence of Grade 3 clinical activity in,
analysis with
creased significantly (P~ 0 . 0 5 chi-square
Yates' correction) (22).
Serial determinations of inhibitory activity were
performed in sera from 21 of the 29 patients with SLE.
Interestingly, of 10 patients who were initially free of
the heat-stable inhibitor, none was found to acquire the
inhibitor despite changes in the activity of their disease
(28 determinations in 10 patients). In contrast, in all of
the patients in whom the heat-stable inhibitor was present initially, inhibitory activity either diminished
markedly or disappeared completely when partial or
complete remission of their disease was achieved (Figure 2). Sera from patients with active disease (Grade 2
or 3) inhibited the chemotactic activity in zymosantreated normal skra by 68.5 & 2.5%. This decreased to
21.2 f 15.6% with complete or partial remission (P
~ 0 . 0 1 Student's
,
t test). In 3 patients, maximum inhibitory activity appeared in sera within 1 week of an episode of infection and coincidentally with an exacerbation of their SLE. The inhibitor subsequently
disappeared from the sera of these patients when their
disease activity was controlled with corticosteroid therapy. Two of these patients were not receiving corticosteroids, and the third was receiving 20 mg of prednisone
PEREZ ET AL
1330
Table 4. Clinical and laboratory findings in patients with SLE
Chemotactic activity in
zymosan-treated sera*
~~
Age, years
Duration of disease, years
Erythrocyte sedimentation ratet
Serum C3, mg/dl$
Serum C4, mg/dl$
Prednisone therapy, &day
Disease activity (number of patients)
Grade 0
Grade I
Grade 2
Grade 3
~
Abnormal
Normal
34.5 f 11.0
2.4 f 3.1
71.4 f 37.2
85.3 f 48.7
20.6 f 13.8
19.9 f 25. I
34.6 f 10.7
4.1 f 4.9
59.9 f 36.8
82.0 f 36.7
3 I .3 f 22.4
3 I .2 f 23.9
0
2
4
7
0
I
12
3
Values are mean f SD.
t Westergren (mm/hour).
+ Normal values for C3 = 93 f 21; C4 = 26 f 8.
daily when infection and maximum inhibitory activity
were documented.
Elevated levels of heat-labile CFI activity in sera
from 3 patients remained constant in multiple determinations and did not appear to correlate with either disease activity or episodes of bacterial infection. Interestingly, all 3 patients with elevated levels of CFI in
their serum were anergic (23-26).
Incidence of infections. Episodes of bacterial infection were recorded in both groups of patients. All infections were documented clinically and by bacteriologic cultures, and all responded to appropriate
antimicrobial therapy. Presumed viral infections were
not tabulated due to insufficient documentation by culture or serology. Only those infections that occurred
within 2 weeks of examining sera (initial or followup
samples) for chemotactic activity were considered. Bacterial infections were documented in 7 of the 13 patients
whose sera yielded abnormal chemotactic activity after
treatment with zymosan (Table 5). Sera from all 7 patients contained the heat-stable inhibitor of C5-derived
chemotactic activity. Serum from 1 patient also contained elevated levels of CFI (Table 3). Of these 7 patients, 3 were not receiving therapy with corticosteroids
at the time that infection was documented. Two other
patients were receiving less than 20 mg of prednisone
daily, while the remaining 2 were receiving 40 mg and
60 mg of prednisone a day, respectively. No patients
were receiving therapy with other immunosuppressive
or cytotoxic agents. The 4 patients in this group in
whom bacterial infections were not documented were
receiving therapy with corticosteroids in doses ranging
from 20 to 60 mg of prednisone daily. Serum levels of
complement (C3 and/or C4) were moderately reduced
in only 3 patients at the time that infection was documented.
Only one episode of infection was recorded
among the group of SLE patients whose sera contained
normal chemotactic activity after treatment with zymosan (P <0.02, chi-square analysis with Yates' correction). A urinary tract infection developed in a patient
receiving 60 mg of the prednisone daily as therapy for
cutaneous vasculitis. All patients in the group with nor
ma1 serum chemotactic activity were receiving corticosteroids at the time that the determinations were performed. Two were receiving less than 10 mg of prednisone a day, 3 were being treated with prednisone in
doses ranging from 15 to 25 mg daily, and the remainder were receiving greater than 30 mg of prednisone
daily.
DISCUSSION
We have found subnormal amounts of chemotactic activity in zymosan-treated &a from 13 of 29
patients with SLE. These results are remarkably similar
to those reported previously by Clark et a1 (10). These
investigators noted significantly reduced amounts of
chemotactic activity in endotoxin-activated sera from 10
of 23 patients with SLE, and they suggested as one pos-
*
c
.100
>
.c
1
V
4
V
.c
0
0
c
0
E
c
W
0
.c
0
c
0
.c
.-
5
c
c
c
c
0)
0
L
a
D
0
Active Disease
Partial or
Complete Remission
Figure 2. Relation between heat-stable inhibitory activity in SLE sera
and degree of clinical disease activity. Assay conditions were the-same
as those described in the legend of Figure I .
1331
INFECTION IN SLE PATIENTS
Table 5. SLE patients with abnormal chemotactic activity in zymosan-activated sera
Patient
DS
LM
PG
RJ
LN
JH
EL*
AJ
MC
cs
AT
MR*
IV*
Age,
years
18
46
28
28
49
50
41
35
23
45
38
22
23
Duration of
disease,
years
Activity of
disease,
grade
Prednisone,
mg/day
C3,
mg/dl
0.6
2
5
3
3
3
3
3
2
3
2
2
2
3
I
1
None
10
60
None
40
None
20
None
6
16
60
2.5
45
56
21
1
1
2
2
2
I2
1.5
0.6
2.5
4
100
31
154
160
144
120
98
30
100
87
a,
mg/dl
4
15
39
4
32
48
20
I4
16
4
24
52
Infection
Streptococcus viridans septicemia
Listeria monocytogenes septicemia
Stophylococcus aureus septicemia
Staphylococcus oureus cellulitis
Escherichio coli pyelonephritis
Diplococcuspneumonioe pneumonia
Diplococcuspneumoniae pneumonia
None
None
None
None
None
None
Serum contained heat-labile CFI activity EL serum and sera from the other patients contained the heat-stable inhibitor of C5-derived
chemotactic activity.
sible explanation for this abnormality the presence in
some SLE serum of either inhibitors or inactivators of
chemotactic factors. We have found this explanation to
be correct and have documented the presence in sera
from 11 patients with SLE of a uniquely specific, heatstable inhibitor of CS-derived chemotactic activity. As
we have reported previously (1 l), this inhibitor does not
affect the motility of normal PMN but acts reversibly on
CS-derived peptides in such a fashion as to interfere
with expression of chemotactic activity. We have successfully isolated and purified this inhibitor from the
sera of several patients with SLE (27) and have found it
to be a highly cationic protein with a molecular weight
of 69,000, as determined by polyacrylamide gel electrophoresis. Its precise identity, however, is as yet unknown.
Sera from 3 patients with SLE were found to
contain elevated levels of nonspecific, heat-labile chemotactic factor inactivator (CFI) activity (12). Serum
from 1 patient contained the heat-stable inhibitor as
well as elevated levels of CFI. Our assay conditions precluded detection of minor elevations of normal serum
CFI activity. Elevated levels of CFI activity have been
reported previously in patients with sarcoidosis (23),
Hodgkin's disease (24), hepatic cirrhosis (25), and lepromatous leprosy (26). Only incidentally have elevated
levels been noted in patients with SLE (1 1,28). Neither
the heat-stable inhibitor nor elevated levels of CFI activity were detected in sera from 21 healthy control subjects, 17 non-SLE patients with systemic bacterial infections, or 18 patients with RA. The patients with RA all
had active polyarticular disease and were being treated
only with nonsteroidal antiinflammatory agents. None
of these patients was febrile and none had prominent
extraarticular manifestations of RA at the time of the
study.
Patients with SLE whose sera contained the
heat-stable inhibitor of CS-derived chemotactic peptides had more active disease clinically but otherwise
were indistinguishable from patients without the inhibitor. When examined initially, the two groups were
comparable with respect to age, duration of disease,
serum levels of complement (C3 and C4), and therapy
with corticosteroids. Although some patients in both
groups had evidence of SLE nephritis, none was significantly azotemic at the time of the study. Abnormal generation of chemotactic activity in sera from patients
with renal failure has been reported previously (29).
When the patients with the heat-stable inhibitor improved clinically (generally in response to therapy with
corticosteroids), this usually was accompanied by a decrease in serum inhibitory activity. It is unclear why the
converse was not observed in the group of SLE patients
without the inhibitor. It is quite possible, however, that
this occurred by chance alone since sera from only 10
patients in this group were examined serially (28 determinations). Furthermore, none of these 10 patients was
examined when they had Grade 3 disease activity. It is
not possible to conclude from these data whether
changes in serum inhibitory activity were, in fact, mediated directly by therapy with corticosteroids or merely
paralleled changes in clinical disease activity.
Complement-derived chemotacticpeptides probably are essential for normal host defenses against invading microorganisms (30,31). consequently, inhibitors or inactivators of such chemotactic peptides might
PEREZ ET AL
1332
be expected to affect host defenses adversely and
thereby contribute to an increased susceptibility to bacterial infections. Our data suggest that this may be the
case in some patients with SLE. We observed only one
episode of bacterial infection among a group of 16 patients with SLE whose sera contained normal amounts
of chemotactic activity after activation with zymosan. In
contrast, 7 of 11 patients with SLE whose sera contained the heat-stable inhibitor of CS-derived chemotactic peptides suffered serious bacterial infections.
Three of these patients were not receiving corticosteroids at the time that infection was documented, and 2
patients were receiving less than 20 mg of prednisone
daily. These observations also are in accord with the
findings of Clark et a1 (10) and support the suggestion
made by others (4-9) that some patients with SLE have
an increased susceptibility to bacterial infections independently of corticosteroid therapy. It should be noted
that in 2 untreated patients with SLE, high levels of
heat-stable inhibitory activity were detected initially in
sera obtained one week prior to an episode of bacterial
infection and coincidentally with an exacerbation of
their primary disease. In both patients, serum inhibitory
activity decreased markedly when the clinical activity of
their SLE was subsequently controlled with corticosteroids.
Only 1 of 3 patients with elevated levels of heatlabile CFI activity became infected. Interestingly, this
patient’s serum also contained the heat-stable inhibitor
just prior to the time that infection was documented.
When the clinical activity of her SLE was subsequently
controlled with corticosteroids, heat-stable inhibitory
activity disappeared from her serum while CFI activity
remained unchanged.
It is not possible to establish conclusively in patients with SLE a direct relationship between increased
susceptibility to bacterial infections and the presence in
serum of inhibitors or inactivators of complement-derived chemotactic peptides. There are simply too many
variables to be considered. Nevertheless, our data and
the data of others (10,28) strongly suggest that such a
relationship exists. Furthermore, it is likely that patients
with SLE will be found to have other humoral and cellular defects involving host defense mechanisms that
contribute to their altered susceptibility to infections
caused by bacteria and fungi.
ACKNOWLEDGMENT
We wish to thank Mr. Martin Tanner for performing
the antinuclear antibody and complement determinations.
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