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Complement Factor I Deficiency Associated With Recurrent Meningitis Coinciding With Menstruation
Carolina González-Rubio, PhD;
Antonio Ferreira-Cerdán, MD, PhD;
Isabel M. Ponce, BS;
Javier Arpa, MD, PhD;
Gumersindo Fontán, MD, PhD;
Margarita López-Trascasa, PhD
Arch Neurol. 2001;58:1923-1928.
ABSTRACT
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Background Complement (C) factor I deficiency is a rare
immunodeficiency state frequently associated with recurrent pyogenic
infections in early infancy. This deficiency causes a permanent
uncontrolled activation of the alternative pathway resulting in massive
consumption of C3.
Patient A 23-year-old woman with monthly recurrent
meningitis episodes, mostly in the perimenstrual period, since August
1999. Previously, at age 16 years, she had meningococcal
sepsis, also coinciding with menstruation.
Objectives To study the patient and her family to
elucidate the molecular defects in the pedigree and to
evaluate her clinical evolution.
Results We describe clinical, immunological, and
treatment follow-up during this period. First, we characterized the
existence of a total complement factor I deficiency defined by
undetectable levels by enzyme immunosorbent assay. This total
deficiency was also found in her sister. Her parents and brother had
approximately half of the normal levels. In addition, the patient had
very low levels of C3; factor B; and an important reduction of factor
H, properdin, C5, C7, and C8 complement components. Additional studies
in the patient's sera evidenced high levels of immune complexes
containing C1q and immunoglobulin (Ig) G, as well as C3b/factor H,
C3b/properdin, C3b/IgG, and properdin/IgG complexes. Treatment with
prophylactic antibiotics, antiestrogen medication, plasma
infusions, or intravenous immunoglobulin has been
unsuccessful in avoiding consecutive meningitis episodes.
Conclusion For the first time to our knowledge, these data
present an unusual relationship between meningitis episodes and
menstruation in factor I immunodeficiency.
INTRODUCTION
HEREDITARY deficiency
of factor I is a rare autosomal recessive condition. To date, 33
homozygous individuals from 23 different pedigrees have been
described.1, 2, 3, 4 The molecular basis of the deficiency has
been resolved in only 3 pedigrees.5, 6 The clinical
manifestations usually begin in early childhood and consist essentially
of severe recurrent pyogenic infections mainly caused by Neisseria
meningitidis, Streptococcus pneumoniae, and
Haemophilus influenzae, as well as an increased incidence of
glomerulonephritis and systemic lupus erythematosus–like illness.
Homozygous patients have low levels of complement (C) 3 and factor B,
reduced levels of factor H and, to a lesser extent, of properdin (P)
and the terminal complement components. Heterozygous individuals are
often asymptomatic and have normal C3 and factor B values, with plasma
concentrations of factor I of about 50% of the normal range.
Human complement factor I is a plasma serine
proteinase that plays an essential role in the modulation of the
complement cascade. Factor I cleaves the  ' chains of C4b and C3b and
thereby is involved in the regulation of both the classical and
alternative C pathways. Factor I function is dependent on various
cofactors: the cleavage of C4b requires C4-binding protein (C4bp), and
the cleavage of C3b is dependent on complement factor H.7, 8
Cell-surface molecules such as complement receptor 1 (CD35) and
membrane cofactor protein (CD46) act as factor I cofactors on host
tissues. By its action on C3, factor I prevents formation of the
alternative pathway C3 convertase and thereby regulates the
amplification loop of the alternative pathway. Factor I is an 88-kd
plasma glycoprotein composed of 2
disulfide-linked polypeptide chains (, 50 kd; ß,
38 kd) that circulates in an active form at a concentration
of 30 to 50 µg/mL.9 In the absence of factor I
and/or factor H, there is an uncontrolled formation of C3 convertases,
which results in marked production of C3b, sufficient to provoke
consumptive secondary immunodeficiency of component C3. Low levels of
C3 may impair immune complex metabolism10 and may reduce
phagocytic activity, opsonization, and antibody production induced by
iC3b, C3dg, and C3 cleavage fragments produced after the action of
factor I.11
We describe a Spanish factor I–deficient woman (age 23 years) who has
a history of recurrent meningitis episodes coinciding with the
perimenstrual period for approximately 18 months (February
2001). Her family is also described.
PATIENTS, MATERIALS, AND METHODS
PATIENTS
Serum samples were obtained from all 5 family members, aliquoted, and
immediately frozen at -80°C until use. Informed consent was obtained
from the patient and the other family members.
METHODS
Complement Studies
Serum concentrations of immunoglobulins, C3, C4, and factor B
were measured by nephelometry. Concentrations of C1q (The Binding Site,
Birmingham, England) and C1 inhibitor (C1-INH) (Dade Behring, Marburg,
Germany) were determined by radial immunodiffusion. Circulating immune
complexes (ICs) containing immunoglobulin (Ig) G and C1q were measured
by commercial enzyme immunosorbent assay (ELISA) (Scimedx Corp,
Denville, NJ). Functional activity of the classical
(CH50) and the alternative (AP50) pathway of
complement was measured by hemolytic assays according to standard
procedures.12 C3-nephritic factor (C3-NEF)
activity was measured by hemolytic assay.13 Activities
of C7 and C8 were also measured by hemolytic assays by using
deficient sera from previously diagnosed patients as
described.14 Initial screening for qualitative estimation
of complement components was performed by double immunodiffusion
(Ouchterlony analysis) with polyclonal antibodies against most of the C
components.
Complement Components, Anti–Factor I Autoantibodies, and ICs
Quantitation by ELISA
Further quantification of P, factor H, factor I, and C5 was performed
by sandwich ELISA, all developed in our laboratory. Briefly, plates
were coated overnight with either a purified IgG fraction
from goat anti-P antibodies (1 µg per well) (ATAB; Atlantic
Antibodies, Scarborough, Me), purified IgG from either anti–factor H
or anti–factor I goat antiserum samples (1 µg per well and 2 µg
per well, respectively) (Quidel, Mountain View, Calif), or mouse
monoclonal IgG anti-C5 (40 ng per well) (Quidel). In each
case, purified P, factor H, or factor I protein, or a C5
calibrated serum (Dade Behring), was included for standard
calibration curves. Appropriate serum dilutions from pooled normal
human serum (NHS) and from each member of the family were included.
After an hour incubation, murine monoclonal anti-P (1/2 K diluted)
(Chemicon, Temecula, Calif), anti–factor H (1/8 K diluted) (Quidel),
anti–factor I (1/20 diluted supernatant) (Serotec, Oxford, England),
or goat immunoglobulins anti-C5 (1/1 K diluted) (ATAB) was used as the
detecting antibody.
Anti–factor I autoantibodies (IgG, IgM, or IgA) were also
checked by ELISA by coating purified factor I (50 ng/well)
(Quidel) to the plates. In each case, the reactions were
visualized by the appropriate peroxidase-conjugated antibodies, using
ABTS/H2O2
(2,2'azino-di-[3-ethylbenzthiazolinesulfonate (6)] diammonium
salt/hydrogen peroxide) as substrate.
To detect possible C3/factor H, C3/P, C3/IgG, and P/IgG complexes in
factor I–deficient serum, ELISA was performed. Briefly, plates
were coated with either monoclonal anti-C3 antibody (from A.
Toraño, PhD, Instituto de Salud Carlos III, Madrid, Spain) or
goat purified immunoglobulins anti-P (ATAB), saturated, and then
incubated with NHS or the patient's deficient serum (1/1 K
diluted). To search the molecule eventually bound to the
captured antigen, several antibodies for testing the presence of each
of these complexes in serum samples were added: polyclonal anti–factor
H, rabbit polyclonal anti-C3 (DAKO A/S, Glostrup, Denmark) or
peroxidase conjugated anti-human IgG (Nordic Immunology, Tilburg, the
Netherlands). The reaction was developed with an appropriate
peroxidase secondary antibody where needed.
Western Blot Test
The Western blot test was also performed to verify factor I deficiency.
Briefly, serum samples (1 µL) from all family members were run on
10% SDS-PAGE (sodium dodecylsulfate-polyacrylamide gel
electrophoresis) under nonreducing conditions. After running the
samples, the gel was transferred to a nitrocellulose sheet and the
membrane probed with an anti–factor I polyclonal antibody (1/500
diluted). The reaction was revealed with a
phosphatase-labeled secondary antibody and NBT/BCIP (nitroblue
tetrazolium/5-bromo-4-chloro-3-indolylphosphate) as precipitating
substrate.
RESULTS
CLINICAL HISTORY AND TREATMENT OF THE PATIENT
The proband was in good health until age 11 years when she had
an acute-onset abdominal pain and underwent appendectomy. At age 16
years she had meningococcal sepsis coincident with menstruation. Then
she had recurrent tonsillitis and underwent tonsillectomy 1 year
later. From age 22 years until February
2001, she has had monthly episodes of acute meningitis around the
perimenstrual period (a total of 20 episodes). After the
fourth consecutive meningeal episode, she was studied for a possible
meningeal fistula with no conclusive results, but she underwent
surgical intervention by bifrontal craniotomy to stop possible nasal
cerebrospinal fluid (CSF) loss and to prevent meningitis; however, she
had another meningeal episode. For 4 months the patient was treated
with a daily dose of 500 mg of sodium cefuroxime as prophylactic. After
the fifth episode, she was referred to our hospital as she had low C3
levels. At each episode she was treated with sodium cefotaxime, 2 g
every 4 hours for a minimum of 1 week. She had good evolution while
receiving this treatment and recovered from cephalea and fever in a few
days. After 8 consecutive episodes, and because of the coincidence with
menstruation, she was treated with triptoreline pamoate (3.5 mg, an
antiestrogen drug, the effects of which last for 3 months), but under
this treatment, periodical meningitis continued. Subsequently, she was
also treated with plasma infusions, 25 mL/kg of weight, every 15 days,
but she continued having meningeal episodes. Since all bacterial
cultures of her CSF were sterile, Mollaret meningitis or an
inflammatory situation was considered, and she was treated with daily
corticoids (prednisone, 1.5-mg/kg body weight) owing to allergy to
nonsteroidal anti-inflammatory agents. During this treatment, positive
polymerase chain reaction findings for N meningitidis type B
DNA was found in the CSF, and the patient was treated with penicillin G
benzatine (1.2 million units), and later, after a new meningeal
episode, she was treated with rifampicin, 300 mg twice a day. Three
months after triptoreline treatment, she had normal menstruation and
meningitis periodically continued without being as strictly related
with the menstrual period. To discard allergic or toxic meningitis
owing to medications, provocative tests were performed with the drugs
she habitually received: amoxicillin trihydrate, metamizol magnesic,
and diclofenac sodium (Voltaren; Novartis Farmaceutica SA, Barcelona,
Spain), all test results being negative, with the exception of
diclofenac, which induced a rash reaction owing to her allergy to
nonsteroidal anti-inflammatory agents, without her developing
meningitis. After that, she continued under care at the hospital and
was treated with intravenous  -globulin (Endobulin; Baxter SL,
Valencia, Spain) infusions at the immunomodulatory dose of 1.5 g/kg of
weight every 10 days, but she has continued having meningitis except
during 1 menstrual period. At present, the dose of -globulin has
been reduced to 1 g/kg body weight every 15 days to avoid the
possibility of hyperviscosity syndrome. The patient has recovered from
all the episodes without any sequelae.
ANALYSIS OF CSF FROM MENINGITIS EPISODES
Glucose was diminished and protein levels were highly elevated,
indicating an infectious situation. Leukocytes were raised to 1550 per
mm3 (85% were polymorphonuclear cells and 15%
monocytes). Beta-2-microglobulin was within the normal range.
Bacteriological cultures of CSF were always sterile. In 2 independent
samples of the CSF, DNA from N meningitidis group B was
detected by polymerase chain reaction, but on 3 other samples, it was
negative. Findings for herpes virus in CSF were also negative, and only
once was cytomegalovirus positive by polymerase chain reaction.
FAMILY HISTORY
The patient has 1 sister and 1 brother who are 9 and 5 years younger,
respectively. Both of them have no history of increased susceptibility
to infections. Her parents are both healthy, and there is no history of
consanguinity although they come from the same village in the south of
Spain. She had another brother who died of meningitis when he was 7
years old (Figure 1).
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Figure 1.
Pedigree, age, and clinical manifestations of the family members and
patient (arrow). Father (I-1), aged 48 years, healthy. Mother
(I-2), aged 42 years, healthy. Daughter 1 (II-1), aged 23 years,
propositus). Son 1 (II-2), died (aged 7 years) from
meningitis. Son 2 (II-3), aged 17 years, asthma. Daughter 2 (II-4),
aged 13 years, healthy.
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IMMUNOLOGICAL STUDIES
Investigation of the patient revealed a normal complete blood
cell count and basic biochemical profile (including
hormones). Lymphocyte markers and function were normal. The
immunoglobulin concentrations were within the normal range, except for
a polyclonal increase of IgM (IgM  500 mg/dL, reference range: 40-260
mg/dL). The IgG subclass concentration gave no evidence of
selective subclass deficiency. Antinuclear antibodies (measured by
indirect immunofluorescence on Hep-2 cells) and rheumatoid
factor (measured by latex agglutination) were not detected.
Other autoantibodies such as anti-myeloperoxidase, anti-proteinase
3, anti-ß2 glycoprotein I, and C3-NEF were not detected. Tetanus and
pneumococcal antibody titers were within the normal range.
Her complement system was investigated together with that of all 4
family members (Table 1). The
results demonstrated the diagnosis of a total factor I deficiency in
the patient and in her asymptomatic younger sister, since factor I was
undetectable by Ouchterlony analysis. This absence was confirmed by
ELISA in both siblings as there was no detectable AP50
and CH50, and both had reduced levels of C3, C5, factor B,
P, and factor H proteins. Activities of C7 and C8 were also reduced in
both siblings. Immune complexes were also elevated in both, although
remarkably higher in the patient. Both parents and her brother had
approximately half the normal concentration of circulating factor I,
together with a slight decrease in AP50 values. All these
data indicated the
inheritance of the trait throughout the family in
an autosomal recessive manner (Figure 1). Western blot
studies are concordant with the diagnosis and showed no other factor I
anomalous species (Figure
2).
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Immune Complexes and Complement Profile of the Family*
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Figure 2.
Factor I antigen detection by Western blot test on the patients' serum
samples. All 5 family members' serum samples were included in
consecutive lanes. Mks indicates molecular weight markers; NHS, normal
human serum. The arrow indicates purified factor I migration.
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COMPLEMENT AND IMMUNE
COMPLEXES ANALYSIS
The different clinical treatments induced some changes; during
plasma infusions, instead of the lack of successful results for
preventing meningitis, C3 plasma values were raised nearly to normal
levels, and AP50 and CH50 were normalized. In
addition, circulating immune complexes were lowered with these
infusions and more so when the patient received corticoids and
rifampicin (data not shown). Intravenous immunoglobulin also
produced a great reduction of these immune complexes (to 30 µg/mL,
reference value, <35 µg/mL). The ELISA experiments
evidenced the presence of C3b/factor H, C3b/P, and P/IgG complexes
(Figure 3). Experimental conditions showed that these complexes were present
throughout the study. These also were found in other patients with
different diseases and the presence of immune complexes, but they were
always negative in the tested controls (n = 10) and in a
serum pool from 30 normal controls.
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Figure 3.
Levels of complement C3/factor H, C3/properdin (P),
C3/immunoglobulin (Ig)G, and P/IgG complexes in patient's (II 1) and
normal human serum (NHS). The mean ± SD
optical density is plotted; n = 5.
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COMMENT
This is the first description to our knowledge of a factor I–deficient
family in Spain, with 23 other pedigrees previously being
described.1, 2, 3, 4 This pedigree presents 1 healthy homozygous
sibling, while to our knowledge, only 2 healthy homozygous siblings
have been previously described.15 Moreover, the homozygous
patient presents a very unusual and dangerous situation owing to the
extraordinary frequency of the meningeal attacks. Factor I deficiency
causes severe secondary C3 and factor B depletion; in addition, the C
profile in this patient showed a
reduction in many other C components such as P,
factor H, C5, C7, and C8. This situation was coincident with other
factor I–deficient patients described earlier.1
Apparently, this patient has all the C components altered with the
exception of the initial classical C components. This profile is
compatible with the excess activation on the fluid phase of the
alternative C pathway. Furthermore, factor I deficiency interferes with
the formation of C3 fragments, which are required for efficient
phagocytosis and B-cell memory (iC3b and C3dg, respectively).
The lack of both types of fragments may also explain the predisposition
for pyogenic infections.1, 2, 3, 4
The patient also presents highly elevated levels of ICs, without any
consumption of the classical C components (C1q or C4). This
feature is uncommon, although the presence of ICs has also been seen in
other factor I–deficient patients.10, 16, 17 In our case,
the presence of C3b/factor H complexes could also be causing the
negative regulation of C3 convertase and producing an increase in C
consumption. Binding of C3b to factor H might act as a mechanism for
the inactivation of some of the biological effects of excess
fluid-phase C3b. Factor H- and C3-altered mobility in agarose
electrophoresis gels has been reported in other factor I–deficient
patients.4, 18 Factor H in the proband's serum migrates
toward the anode with higher mobility than factor H from the normal
control (data not shown). This abnormal migration could
possibly be owing to the formation of these C3b/factor H complexes,
since in the absence of factor I, C3b persists in high levels and may
increase its binding to factor H. Furthermore, taking into account the
predicted existence of C3b/IgG complexes in normal
serum,19, 20 we have shown the presence of these complexes
by ELISA experiments. Results show that C3/P, P/IgG, or C3b/IgG
complexes are present in the serum of this patient at a higher
concentration than in NHS. Moreover, these C components could be
involved in a large molecular complex (C3b/P/IgG) as predicted by Lutz
et al,19 and in agreement with the proposed mechanism,
complexes could preserve this excess of C3b as described by Jelezarova
and Lutz.20
The main causes of recurrent meningitis were taken into account,
and most of them were discarded. A parameningeal focus could never be
evidenced; moreover, cryptococcal cultures were always sterile as were
Borrelia cultures, and the patient never had Behçet
disease. The clinical situation was not like familial Mediterranean
fever since her episodes were benign and clinical symptoms such as
cephalea and fever remitted in 2 to 3 days. The cause of these
meningitides (infectious or Mollaret) is unclear. The possibility that
they were all infectious is scarcely supported since standard
microbiological cultures for CSF were always sterile. Moreover,
polymerase chain reaction was positive twice for N
meningitidis type B DNA and negative 2 more times in 4 different
CSF samples. Furthermore, we could not rule out that some of these were
septic and others aseptic as both types were possible. At each episode,
antibiotics were administered, and the patient's clinical symptoms
diminished with this treatment. We did not obtain results without
antibiotic treatment since the risk of worsening the condition was too
great. Moreover, the patient and family always rejected this option.
Mollaret recurrent meningitis was also found in another factor
I–deficient woman.21
Cerebral endometriosis has been described as being associated with
intermittent focal headaches,22 causing catamenial
epilepsy23 and subarachnoid hemorrhage,24 but
in this patient, meningeal hemorrhage has never been found as the
absence of red cells in the CSF has proven. Moreover, meningeal
episodes have continued in the absence of menstruation as happened with
triptoreline treatment. The eventual relationship of meningitis with
menstruation is unknown. In a different situation, as hereditary
angioedema caused by C1-INH deficiency, hormonal factors can regulate
the episodes of this disease; for example, menstruation could be a
triggering factor for episodes, and pregnancy is also a condition that
can improve or worsen the course of this disease. Furthermore,
androgens such as danazol are used for treating this
angioedema.25, 26 Taking this into account, we can
hypothesize that an unknown factor or mechanism related to hormonal
regulation in this complement deficiency, and meningitis could be an
underlying factor. Some authors have shown that several components of
the complement system exist in the human endometrium in a
hormone-dependent manner and may play a role in the normal reproductive
function.27 Recently, Nowicki et al28 have
shown that there is a higher susceptibility to gonococcal infection by
Neisseria gonorrhoeae during the menstrual cycle, and changes
in antibacterial activity are correlated with serum complement
activity. These authors suggest that similar cyclic changes could be
involved in the pathogenesis of other infectious diseases in women.
Treatment with triptoreline has not abolished the meningeal episodes in
this case, but other hormonal factors could be involved.
In conclusion, we describe a factor I–deficient patient with an
unusually high number of meningeal episodes with resistance to several
treatments, including plasma infusion, anti-inflammatory drugs, and
prophylaxis with antibiotics, the latter being previously suggested in
this3 and other C deficiencies.29 The molecular
basis of this deficiency is being studied to characterize this
patient's genetic defect.
AUTHOR INFORMATION
Accepted for publication July 12, 2001.
This work was partly supported by grant FIS 00/0216 (Fondo de
Investigación Sanitaria, Instituto de Salud Carlos III, Madrid)
and Comunidad Autónoma de Madrid, Madrid, grant 08.6/0028/2000.
Dr González-Rubio is the recipient of a grant from Comunidad
Autónoma de Madrid.
From the Immunology Unit (Drs González-Rubio, Ferreira-Cerdán,
Fontán, and López-Trascasa and Ms Ponce) and Neurology
Service (Dr Arpa), Hospital Universitario, La Paz, Madrid,
Spain.
Corresponding author and reprints: Margarita López-Trascasa, PhD,
Immunology Unit, Hospital Universitario La Paz, Paseo de la Castellana,
261, 28046 Madrid, Spain (e-mail: mlopeztrascasa{at}hulp.insalud.es).
REFERENCES
| |
1. Vyse TJ, Späth PJ, Davies KA, et al. Hereditary complement factor
I deficiency. QJM. 1994;87:385-401.
FREE FULL TEXT
2. Kirschfink M, Binder R. Deficiencies in the alternative pathway:
factors I and H. In: Rother K, Till GO, Hänsch GM, eds. The
Complement System. 2nd ed. New York, NY: Springer-Verlag;
1997:420-427.
3. Leitão MF, Vilela MMS, Rutz R, Grumach AS, Condino-Neto A, Kirschfink M. Complement factor I deficiency in a family with
recurrent infections. Immunopharmacology. 1997;38:207-213.
FULL TEXT
|
ISI
| PUBMED
4. Naked GM, Florido MPC, Ferreira de Paula P, Vinet AM, Inostroza JS, Isaac L. Deficiency of human complement factor I associated with
lowered factor H. Clin Immunol. 2000;96:162-167.
FULL TEXT
|
ISI
| PUBMED
5. Vyse TJ, Morley BJ, Bartok I, et al. The molecular basis of hereditary
complement factor I deficiency. J Clin Invest. 1996;97:925-933.
ISI
| PUBMED
6. Morley BJ, Bartók I, Späth PJ, Vyse TJ, Schneider PM, Walport MJ. Molecular basis of hereditary factor I deficiency [abstract]. Mol Immunol. 1998;35:344.
7. Fujita T, Gigli I, Nussenzweig V. Human C4-binding protein, II: role in
proteolysis of C4b by C3b-inactivator. J Exp Med. 1978;148:1044-1051.
FREE FULL TEXT
8. Pangburn MK, Schreiber RD, Müller-Eberhard HJ. Human C3b
inactivator: isolation, characterization and demonstration of an
absolute requirement for serum protein beta1H for cleavage of C3b and
C4b in solution. J Exp Med. 1977;146:257-270.
FREE FULL TEXT
9. Nilsson B, Nilsson Ekdahl K. Components of the alternative pathway. Rother K, Till GO, Hänsch GM, eds. The Complement
System. 2nd ed. New York, NY: Springer-Verlag; 1997:23-49.
10. Solal-Celigny P, Laviolette M, Hebert J, et al. C3b inactivator deficiency with immune complex manifestations. Clin Exp Immunol. 1982;47:197-205.
ISI
| PUBMED
11. Porteu F, Fischer A, Descamps-Latscha B, Halbwachs-Mecarelli L. Defective complement receptors (CR1 and CR3) on erythrocytes and
leukocytes of factor I (C3b inactivator) deficient patients. Clin
Exp Immunol. 1986;66:463-471.
ISI
| PUBMED
12. Phimister GM, Whaley K. Measurement of complement. In: Gooi HC, Chapel
H, eds. Clinical Immunology: A Practical Approach. Oxford,
England: Oxford University Press; 1990:81-109.
13. Rother U. A new screening test for C3 nephritis factor based on a
stable cell bound convertase on sheep erythrocytes. J Immunol
Methods. 1982;51:101-107.
FULL TEXT
|
ISI
| PUBMED
14. Segurado OG, Arnáiz-Villena A, Iglesias-Casarrubios P, et al. Combined total deficiency of C7 and C4B with systemic lupus
erythematosus. Clin Exp Immunol. 1992;87:410-414.
ISI
| PUBMED
15. Floret D, Stamm D, Ponnard D. Increased susceptibility to infection in
children with congenital deficiency of factor I. Pediatr Infect
Dis J. 1991;10:615-618.
ISI
| PUBMED
16. Møller Rasmussen J, Teisner B, Jepsen HH, et al. Three cases of factor I deficiency: the effect of treatment with plasma. Clin Exp Immunol. 1988;74:131-136.
ISI
| PUBMED
17. Sadallah S, Gudat F, Laissue JA, Späth PJ, Schifferli J-A. Glomerulonephritis in a patient with complement factor I deficiency. Am J Kidney Dis. 1999;33:1153-1157.
ISI
| PUBMED
18. Whan V, Rother U, Rauterberg EW, Day NK, Laurell AB. C3b-inactivator
deficiency: association with an alpha-migrating factor H. J Clin
Immunol. 1981;4:228-233.
19. Lutz HU, Stammler P, Jelezarova E, Nater M, Späth PJ. High doses
of immunoglobulin G attenuate immune aggregate-mediated complement
activation by enhancing physiologic cleavage of C3b in
C3bn-IgG complexes. Blood. 1996;88:184-193.
FREE FULL TEXT
20. Jelezarova E, Lutz HU. Assembly and regulation of the
complement amplification loop in blood: the role of C3b-C3b-IgG
complexes. Mol Immunol. 1999;36:837-842.
FULL TEXT
|
ISI
| PUBMED
21. Bonnin AJ, Zeitz HJ, Gewurz A. Complement factor I deficiency with
recurrent aseptic meningitis. Arch Intern Med. 1993;153:1380-1383.
ABSTRACT
22. Thibodeau LL, Prioleau RG, Manuelidis EE, Merino MJ, Heafner MD. Cerebral endometriosis: case report. J Neurosurg. 1987;66:609-610.
ISI
| PUBMED
23. Ichida M, Gomi A, Hiranouchi N, et al. A case of cerebral endometriosis
causing catamenial epilepsy. Neurology. 1993;43:2708-2709.
FREE FULL TEXT
24. Duke R, Fawcett P, Booth J. Recurrent subarachnoid hemorrhage due to
endometriosis. Neurology. 1995;45:1000-1002.
ABSTRACT
25. Frank MM, Gelfand JA, Atkinson JP. Hereditary angioedema: the clinical
syndrome and its management. Ann Intern Med. 1976;84:580-593.
26. Agostoni A, Cicardi M. Hereditary and acquired C1-inhibitor deficiency:
biological and clinical characteristics in 235 patients. Medicine. 1992;71:206-215.
PUBMED
27. Hasty LA, Lambris JD, Lessey BA, Pruksananonda K, Lyttle CR. Hormonal
regulation of complement components and receptors throughout the
menstrual cycle. Am J Obstet Gynecol. 1994;170:168-175.
ISI
| PUBMED
28. Nowicki S, Tassell AH, Nowicki B. Susceptibility to gonococcal
infection during the menstrual cycle. JAMA. 2000;283:1291-1292.
FREE FULL TEXT
29. Potter PC, Frasch CE, van der Sande WJ, Cooper RC, Patel Y, Orren A. Prophylaxis against Neisseria meningitidis infections and
antibody responses in patients with deficiency of the sixth component
of complement. J Infect Dis. 1990;161:932-937.
ISI
| PUBMED
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Clin. Microbiol. Rev. 2008;21:519-537.
ABSTRACT
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Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome
de Jorge et al.
Proc. Natl. Acad. Sci. USA 2007;104:240-245.
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Mutations in Complement Factor I Predispose to Development of Atypical Hemolytic Uremic Syndrome
Kavanagh et al.
J. Am. Soc. Nephrol. 2005;16:2150-2155.
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Predisposition to atypical hemolytic uremic syndrome involves the concurrence of different susceptibility alleles in the regulators of complement activation gene cluster in 1q32
Esparza-Gordillo et al.
Hum Mol Genet 2005;14:703-712.
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