Antibodies to periodontogenic bacteria are associated with higher disease activity in lupus patients
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Antibodies to periodontogenic bacteria are associated
with higher disease activity in lupus patients
H. Bagavant, M.L. Dunkleberger, N. Wolska, M. Sroka, A. Rasmussen, I. Adrianto*,
C. Montgomery, K. Sivils, J.M. Guthridge, J.A. James, J.T. Merrill, U.S. Deshmukh
Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, USA;
*
Current affiliation: Department of Public Health Sciences, Henry Ford Health System, Detroit, USA.
Abstract
Objective
Microbial infections and mucosal dysbiosis influence morbidity in patients with systemic lupus erythematosus (SLE).
In the oral cavity, periodontal bacteria and subgingival plaque dysbiosis provide persistent inflammatory stimuli at the
mucosal surface. This study was undertaken to evaluate whether exposure to periodontal bacteria influences disease
parameters in SLE patients.
Methods
Circulating antibodies to specific periodontal bacteria have been used as surrogate markers to determine an ongoing
bacterial burden, or as indicators of past exposure to the bacteria. Banked serum samples from SLE patients in the
Oklahoma Lupus Cohort were used to measure antibody titres against periodontal pathogens (Aggregatibacter
actinomycetemcomitans, Porphyromonas gingivalis, and Treponema denticola) and commensals (Capnocytophaga
ochracea, and Streptococcus gordonii) by ELISA. Correlations between anti-bacterial antibodies and different clinical
parameters of SLE including, autoantibodies (anti-dsDNA, anti-SmRNP, anti-SSA/Ro and anti-SSB/La), complement,
and disease activity (SLEDAI and BILAG) were studied.
Results
SLE patients had varying amounts of antibodies to different oral bacteria. The antibody titres against A. actinomycetem-
comitans, P. gingivalis, T. denticola, and C. ochracea were higher in patients positive for anti-dsDNA antibodies, and
they showed significant correlations with anti-dsDNA titres and reduced levels of complement. Among the periodontal
pathogens, only antibodies to A. actinomycetemcomitans were associated with higher disease activity.
Conclusion
Our results suggest that exposure to specific pathogenic periodontal bacteria influences disease activity in SLE patients.
These findings provide a rationale for assessing and improving periodontal health in SLE patients, as an adjunct to
lupus therapies.
Key words
systemic lupus erythematosus, periodontitis, antibodies
Clinical and Experimental Rheumatology 2019; 37:Clinical
106-111.and Experimental Rheumatology 2019Periodontal bacterial exposure and lupus / H. Bagavant et al.
Harini Bagavant, MBBS, PhD Introduction ing higher incidence of periodontitis
Micah L. Dunkleberger, BA Systemic lupus erythematosus is a in SLE patients (11). In addition, a
Nina Wolska, MS complex autoimmune disorder affect- recent report on the characterisation of
Magdalena Sroka, MS
ing multiple organ systems such as the the subgingival microbial community
Astrid Rasmussen, MD, PhD
Indra Adrianto, PhD skin, kidneys, heart, lung, and brain (1). showed that compared to non-lupus
Courtney Montgomery, PhD The presence of autoantibodies against controls, SLE patients have significant
Kathy Sivils, PhD multiple self-components is a hall mark dysbiosis in the periodontal microbiota,
Joel M. Guthridge, PhD of SLE and the autoantibody specifici- with a greater proportion of pathogenic
Judith A. James, MD, PhD ties are associated with distinct patho- bacteria (12). Whether exposure to the
Joan T. Merrill, MD logic features of the disease. In addi- periodontal bacteria affects disease ac-
Umesh S. Deshmukh, PhD
tion to a strong genetic predisposition, tivity in SLE is still not clear. The goal
Please address correspondence to: environmental factors, particularly in- of the present study was to determine if
Dr Harini Bagavant,
fectious agents, can play a role in SLE bacteria in the dental plaque influence
Research Associate Member,
Oklahoma Medical Research Foundation, pathogenesis. In SLE, microbes hold autoimmune features in SLE patients.
825 NE 13th Street, the potential to initiate and exacerbate Since high titres of IgG antibodies to
Oklahoma City, OK 73104, USA autoimmunity, and modify the course plaque bacteria indicate either an ongo-
E-mail: harini-bagavant@omrf.org of clinical disease by affecting multiple ing infection or prior history of expo-
Reprints will not be available from the pathways (2). sure (13-16), banked sera from a well
author. The association between antibodies to characterised SLE patient cohort were
Received on January 2, 2018; accepted infectious agents and antibodies to self- analysed for antibodies to a selected
in revised form on April 17, 2018. proteins has been established in a wide panel of oral bacteria. The associations
© Copyright Clinical and spectrum of autoimmune diseases (3, 4). between anti-bacterial antibodies and
Experimental Rheumatology 2019. Over the past several years, considera- clinical disease were evaluated.
ble attention has been directed towards
investigating how viral exposures, such Methods
as Epstein Barr virus, influence the dis- Patients and controls
ease (5). However, bacterial infections All experiments were performed in ac-
affecting the respiratory tract, urinary cordance with the Helsinki Declaration
tract, and skin are often seen in SLE pa- and approved by the Oklahoma Medi-
tients (6). In addition to these anatomic cal Research Foundation Institutional
sites, the gingival mucosal surface is Review Board. Banked serum samples
continuously exposed to a plethora of and clinical data were obtained from
bacteria present in the dental plaque. SLE patients seen from May 2002 to
The interface between the dental plaque October 2014 in the Oklahoma Lupus
and the gingival epithelium represents Cohort through the Oklahoma Rheu-
a site of constant communication be- matic Diseases Research Cores Cent-
tween microbes and the innate immune er. Patients who met the ≥4 American
system (7). Further, these bacteria College of Rheumatology (ACR) SLE
have access to the systemic circulation criteria, and were evaluated for disease
through bleeding gums and through di- activity (n=303) were studied. The de-
rect invasion of the gingival epithelium mographics of the patients in this study
(8, 9). Previous work from our labora- are shown in Table I. Sera from de-
tory suggests that the dental plaque can identified volunteers, who did not have
offer a chronic source of autoantigen SLE were also studied for anti-bacterial
mimics (10). T cells reactive with a antibodies (n=75).
Sjögren’s syndrome and lupus-associ-
ated autoantigen Ro60, can be activated Clinical parameters of SLE
by peptides derived from dental plaque Anti-dsDNA antibody was measured
bacteria. Thus, exposure of the immune by the Crithidia luciliae indirect im-
Funding: this work was supported by system to dental plaque bacteria in SLE munofluorescence assay. Antibodies to
grants from the Oklahoma Center for the
patients holds a significant potential to other autoantigens including Sm pro-
Advancement of Science and Technology
(HR15-145), and the National Institutes modulate the disease. tein with ribonucleoproteins (SmRNP),
of Health (P30GM110766, The knowledge of lupus patient re- Sjögren’s syndrome antigen A (SSA/
U54GM104938, P30AR053483, sponses to dental plaque bacteria is lim- Ro), and Sjögren’s syndrome antigen
P30GM103510, U19AI082714, ited. The indication that lupus patients B (SSB/La) were measured using a
and U01AI101934). are exposed to these bacteria can be bead-based assay. C3 and C4 comple-
Competing interests: none declared. derived indirectly from reports show- ment levels were determined at the
Clinical and Experimental Rheumatology 2019 107Periodontal bacterial exposure and lupus / H. Bagavant et al.
Table I. Oklahoma Lupus Cohort patient
demographics.
SLE patients
Total, n 303
Female, n (%) 279 (92.1)
Age in years, median (range) 40 (16-71)
Duration of disease in years, 2 (0-39)
median (range)
Race, n (%)
Caucasian 165 (54.5)
African American 62 (20.5)
Asian 12 (3.9)
American Indian 41 (13.5)
Mixed (2 or more) 22 (7.2)
Pacific Islander 1 (0.3)
ACR SLE criteria, median (range) 6 (4-11)
SLEDAI, median (range), n 6 (0-24), 300
BILAG total, median (range), n 11 (0-42), 303
Diagnostic Laboratory of Oklahoma.
Clinical assessments of SLE were done
using the modified SELENA - Sys-
temic Lupus Erythematosus Disease
Activity Index (SLEDAI) (17) and the
British Isles Lupus Assessment Group
(BILAG-2004) Index (18).
Bacterial strains
Bacterial strains residing in the sub-
gingival plaque in the oral cavity were
used as antigens for ELISA, and were
obtained from ATCC (Manassas, VA,
USA). These include: red complex or-
ganisms implicated in chronic periodon-
tal disease: Prophyromonas gingivalis
(ATCC 33277) and Treponema denticola
(ATCC 35405); a periodontal pathogen
associated with aggressive periodontal
disease: Aggregatibacter actinomycet-
emcomitans serotype b (ATCC 28522);
and commensal bacteria: Streptococcus
gordonii (ATCC 51656) and Capnocy-
tophaga ochracea (ATCC 33596).
Detection of antibody to
bacterial strains
An ELISA-based assay to measure anti-
bacterial antibodies was used as previ-
ously described (19). Sera from the
Oklahoma Lupus Cohort were tested
at 1:500 dilution. Serial dilutions of a Fig. 1. Presence of anti-dsDNA antibody in SLE patients is associated with higher antibody titres
pooled serum sample were included as against A. actinomycetemcomitans, P. gingivalis, T.denticola and C. ochracea.
(A-E) SLE patients were stratified into autoantibody positive or autoantibody negative groups based
a calibrator for each plate. A standard on reactivity to dsDNA, SmRNP, SSA/Ro, and SSB/La respectively and anti-bacterial antibody titres
curve was constructed and anti-bacte- were compared using Kruskal Wallis test. Dunn’s post-test was used to compare anti-bacterial antibod-
rial antibody titres (units/ml) were cal- ies between autoantibody positive and negative groups for each specificity. Anti-bacterial antibody
culated for each sample. Samples with titres are plotted as units/ml (median+interquartile range); (n) number of patients in each group.
(F-I) Correlation between anti-dsDNA titres and anti-bacterial antibody titres calculated by Spearman
OD readings higher than the calibration method.
curve were re-tested at higher dilutions.
108 Clinical and Experimental Rheumatology 2019Periodontal bacterial exposure and lupus / H. Bagavant et al.
Table II. Association of antibodies to periodontal bacteria and disease activity by SLEDAI. tients, anti-A. actinomycetemcomitans
antibodies showed the strongest cor-
Bacteria Antibody titres (n) SLEDAI SCORES
relation (Spearman rho=0.57; p10 p-value* with anti-dsDNA antibody titres (Fig-
A.actino- median 1618 2021# 2318## 0.011 ure 1f). Anti-P. gingivalis (rho=0.42;
mycetemcomitans range 17-14520 275-21855 456-60160 p=0.005), anti-T. denticola (rho=0.43;
(n) (63) (184) (53) p=0.004) and anti-C. ochracea
P. gingivalis median 2823 3616 6062### 0.0095 (rho=0.34; p=0.04) also showed statis-
range 525-13550000 268-48470 225-88350
(n) (62) (179) (52) tically significant, albeit more modest
T. denticola median 7524 8505 9903 0.15 correlations (Fig. 1g-i).
range 894-94190 845-149900 1046-172500
(n) (61) (179) (51) Antibodies to specific periodontal
C.ochracea median 3929 4668 4383 0.07 pathogens correlate with indicators of
range 943-24030 677-122500 714-107800
(n) (54) (160) (37) higher disease activity in SLE patients
S.gordonii median 9999 9848 9562 0.86 SLE patients were categorised based
range 1393-30840 1630-45610 1826-32980 on disease activity into mild (SLEDAI
(n) (62) (179) (52) ≤2), moderately severe (SLEDAI 3-9)
*by Kruskal Wallis test; #p=0.04, ##
p=0.007, ###p=0.0047 by Dunn’s post-test. and severe (SLEDAI ≥10) groups. As
shown in Table II, a comparison of anti-
Table III. Association of antibodies to periodontal bacteria and disease activity by BILAG. bacterial antibody titres between these
3 groups showed a statistically signifi-
Bacteria Antibody titres (n) TOTAL BILAG cant association between increased dis-
Mild Mod. Severe to severe p-value ease activities with higher anti-A. actin-
(C/D) (≥3B or ≥1A) omycetemcomitans antibody (p=0.011)
and higher anti-P. gingivalis antibody
A. actinomycetemcomitans median 1794 2534 0.043
range 17-16960 350-21855 titres (p=0.0095).
(n) (90) (43) The anti-A. actinomycetemcomitans an-
P. gingivalis median 3408 5026 0.056 tibody titres in patients with the lowest
range 572-307000 307-88350 disease activity scores were significant-
(n) (90) (43)
ly lower than the patients with moderate
T. denticola median 8066 10565 0.23
range 893-149900 1922-80900 (p=0.04) or highest activity (p=0.007).
(n) (90) (42) Anti-P. gingivalis antibodies were sig-
C. ochracea median 4197 5369 0.08 nificantly lower in the patients with
range 943-122500 761-95120 lowest disease activity compared to the
(n) (76) (35)
highest activity scores (p=0.0047).
S. gordonii median 10012 9907 0.46
range 1393-45610 3528-25180 The British Isles Lupus Assessment
(n) (90) (43) Group (BILAG) index uses different
clinical measures for evaluation of dis-
Statistical analyses based on the presence or absence of an- ease activity based on individual organ
Graph Pad Prism 7.0 and Systat software tibodies to the major lupus-associated involvement (18). The disease activity
were used to perform statistical analyses. autoantigens: dsDNA, Sm/RNP, SSA/ in each patient was classified as mild
Normality tests were performed on each Ro, and SSB/La. The anti-bacterial (only C and D organ scores; n=90),
dataset and non-parametric tests were antibody titres in the antibody positive moderate (1- or 2- B scores; n=168),
used for non-Gaussian distributions. and negative group for each autoantigen and moderately severe to severe (≥3- B
Mann-Whitney test was used to compare were compared. As shown in Figure or ≥1- A score; n=43). As shown in Ta-
two populations; Kruskal-Wallis test fol- 1a-e, patients with anti-dsDNA have ble III, the anti-A. actinomycetemcomi-
lowed by Dunn’s post-test for multiple higher antibodies to A. actinomycet- tans antibody titres were significantly
comparisons. Correlations were deter- emcomitans, P. gingivalis, T. denticola, higher in patients with moderately se-
mined by Spearman’s method. A p-value and C. ochracea, but not to S. gordonii, vere to severe activity compared to the
of less than 0.05 at a 95% confidence in- when compared to patients lacking anti- patients with mild disease (p=0.043).
terval was considered significant. dsDNA. The presence of anti-SmRNP A similar trend was seen in anti-P.
antibodies was associated with higher gingivalis antibody titres, although it
Results anti-bacterial antibody titres against all failed to reach statistical significance
Higher anti-bacterial antibody titres the bacteria, while anti-SSA and anti- (p=0.056). Associations were not seen
against specific bacteria are associated SSB failed to associate with antibodies between disease activity and antibody
with the presence of anti-dsDNA to any of the periodontal bacteria. titres to T. denticola, C. ochracea or S.
Patients were stratified into groups Among the anti-dsDNA positive pa- gordonii.
Clinical and Experimental Rheumatology 2019 109Periodontal bacterial exposure and lupus / H. Bagavant et al.
ing high titre of antibodies against or- actinomycetemcomitans antibody titres
ganisms associated with periodontitis and increased disease activity with both
in our cohort of SLE patients suggests SLEDAI and BILAG indices. Higher
that the patients immune system was ex- anti-P. gingivalis antibody titres were
posed to these oral pathogens. also strongly associated with higher
The presence of anti-dsDNA antibody SLEDAI scores. Anti-dsDNA antibod-
is a hallmark of SLE, and it showed ies are a scoring criterion for SLEDAI,
strongest correlation with anti-A. ac- and multivariate analyses showed that
tinomycetemcomitans. Although the the SLEDAI association with anti-P.
precise specificity of anti-A. actinomy- gingivalis antibodies was significantly
Fig. 2. Limited cross reactivity between anti-A. cetemcomitans antibodies is not known, driven by anti-dsDNA positivity. How-
actinomycetemcomitans and anti-dsDNA antibod- they do not appear to cross-react with ever, this fails to explain the trend be-
ies in SLE patients. IgG purified from five SLE DNA. While absorption of anti-A. actin- tween higher P. gingivalis antibodies
patients were pre-absorbed with A. actinomycet-
emcomitans, and the residual antibodies to A. ac-
omycetemcomitans IgG with A. actino- and higher BILAG indices. Further,
tinomycetemcomitans (A) and dsDNA (B) were mycetemcomitans significantly reduced despite the comparable association of
measured by ELISA. Sera not pre-absorbed with anti-bacterial reactivity, it failed to re- anti-T. denticola antibodies with higher
A. actinomycetemcomitans were used as controls.
Each line connects control and A. actinomycet-
duce dsDNA reactivity (Fig. 2). These anti-dsDNA as well as, C3 and C4 com-
emcomitans absorbed serum for the same patient. data suggest that the A. actinomycetem- plement depletion (Supplementary Fig.
p-values were calculated by paired t-test. comitans mediated periodontal disease 2), there was a lack of association be-
process might contribute towards am- tween anti-T. denticola antibodies and
Discussion plifying anti-dsDNA in SLE patients. either measure of disease activity. An
By using banked serum samples from This is highly plausible considering the important factor to consider is that the
a well characterised cohort of SLE pa- study by Konig et al which implicates A. BILAG and SLEDAI are very different
tients, this study demonstrates that high actinomycetemcomitans as a trigger for kinds of measurement. While SLEDAI
titre of IgG antibodies against the perio- rheumatoid arthritis (24). scores are more affected by global in-
dontal pathogen A. actinomycetemcom- We had previously reported that bacte- creases in disease activity, the BILAG
itans was significantly associated with rial proteins from oral commensal bac- index is more sensitive and fluctuates
higher disease activity in SLE patients. teria, specifically C. ochracea were ca- with changes even in an individual
Considered together with previous re- pable of activating T cells reactive with manifestation of the disease. Taken to-
ports investigating the association be- the Sjögren and lupus associated autoan- gether, these results suggest the need
tween periodontal disease and lupus tigen, SSA/Ro60. Therefore, the lack of for additional studies to investigate the
(20-23), our study supports the notion association between antibodies to peri- contribution of exposure to P. gingivalis
that bacterial infections in the subgingi- odontal bacteria and SSA and SSB was a in SLE. The present study suggests that
val mucosa modulate SLE. surprising result. Since SSA and/or SSB the relationship between SLE and peri-
In this study we used the presence of antibody positivity was significantly as- odontal disease is defined by the specif-
circulating anti-bacterial antibodies as sociated with the history of sicca or dry ic pathogen, A. actinomycetemcomitans
evidence for exposure to the bacteria. mouth in our lupus patients (p=0.015, driving the periodontal disease.
This strategy is well established and n=299), anti-bacterial antibodies were A unique characteristic of A. actinomy-
antibody titres against bacteria from the compared between patients with or cetemcomitans is their ability to induce
subgingival plaque have been used as without sicca. As shown in Supplemen- citrullination of host proteins. A recent
indicators for exposure to and burden of tary Fig. 1, anti-bacteria antibody titres report showed that Leukotoxin A, an
specific bacteria (13-16). A recent study between patients with or without sicca exotoxin produced by A. actinomycet-
showed a strong correlation between the were not significant. These results sup- emcomitans, induces permiabilisation
detection of antibodies to A. actinomy- port previous literature showing lack of the cell plasma membranes leading
cetemcomitans and its leukotoxin with of association between clinical and to an unregulated influx of calcium in
the presence of A. actinomycetemcomi- microbiologic parameters of periodon- toxin susceptible cells (24, 31). This
tans in the sub-gingival isolates from tal disease and Sjögren’s syndrome, a activates the endogenous protein argi-
individual patients (24). Further, anti-A. disease characterised by reduced saliva nine deiminase (PAD) enzymes in the
actinomycetemcomitans and anti-P. gin- production and progressive loss of sali- cytosol (PAD2) and the nucleus (PAD4)
givalis antibody titres reflecting expo- vary gland function (27-29). In contrast and causes hypercitrullination of self-
sure to those bacteria are known to per- to periodontal disease, lack of saliva has proteins, which in neutrophils, leads
sist for 15 years (25). A similar clinical been found to be strongly associated to cell death. Thus, exposure to A. ac-
observation was also made in another with dental caries and supra-gingival tinomycetemcomitans and not the other
study where elevated titres of anti-P. bacteria, which are distinct from the periodontal pathogens in lupus patients
gingivalis antibodies persisted when periodontal bacterial populations (30). holds the potential to amplify a patho-
monitored for 24 months even when the Our clinical analyses showed a signifi- genic autoimmune response through the
disease was inactive (26). Thus, detect- cant association between higher anti-A. release of modified self-antigens.
110 Clinical and Experimental Rheumatology 2019Periodontal bacterial exposure and lupus / H. Bagavant et al.
This is a cross sectional study, and there- References 17. PETRI M, KIM MY, KALUNIAN KC et al.:
Combined oral contraceptives in women with
fore it does not allow us to postulate 1. KAUL A, GORDON C, CROW MK et al.:
Systemic lupus erythematosus. Nat Rev Dis systemic lupus erythematosus. N Engl J Med
causal associations between periodontal Primers 2016; 2: 16039. 2005; 353: 2550-8.
bacterial exposure and SLE. Further, in 2. BOGDANOS DP, SMYK DS, RIGOPOULOU EI, 18. YEE CS, FAREWELL V, ISENBERG DA et al.:
a study of this size, the heterogeneous SAKKAS LI, SHOENFELD Y: Infectomics and Revised British Isles Lupus Assessment
autoinfectomics: a tool to study infectious-in- Group 2004 index: a reliable tool for assess-
medications given to the patients, and ment of systemic lupus erythematosus activ-
duced autoimmunity. Lupus 2015; 24: 364-73.
the lack of this information prevents 3. KIVITY S, AGMON-LEVIN N, BLANK M, ity. Arthritis Rheum 2006; 54: 3300-5.
the ability to make proper adjustments SHOENFELD Y: Infections and autoimmun- 19. CRAIG RG, BOYLAN R, YIP J et al.: Serum
of data for treatment. It is possible that ity--friends or foes? Trends Immunol 2009; IgG antibody response to periodontal patho-
30: 409-14. gens in minority populations: relationship to
immune modulators may influence peri- periodontal disease status and progression. J
4. AGMON-LEVIN N, DAGAN A, PERI Y et al.:
odontal bacteria, and future studies with The interaction between anti-Ro/SSA and anti- Periodontal Res 2002; 37: 132-46.
medication controlled protocols will be La/SSB autoantibodies and anti-infectious 20. RHODUS NL, JOHNSON DK: The prevalence
helpful. The sera were obtained from antibodies in a wide spectrum of auto-immune of oral manifestations of systemic lupus ery-
diseases: another angle of the autoimmune thematosus. Quintessence Int 1990; 21: 461-5.
samples banked over an extended period 21. FERNANDES EG, SAVIOLI C, SIQUEIRA JT,
mosaic. Clin Exp Rheumatol 2017; 35: 929-35.
of time and therefore, retroactive dental 5. POOLE BD, SCOFIELD RH, HARLEY JB, SILVA CA: Oral health and the masticatory
information and periodontal health in the JAMES JA: Epstein-Barr virus and molecular system in juvenile systemic lupus erythema-
patient and control populations were not mimicry in systemic lupus erythematosus. tosus. Lupus 2007; 16: 713-9.
Autoimmunity 2006; 39: 63-70. 22. TIETMANN C, BISSADA NF: Aggressive peri-
available. This lack of data precluded the 6. DOATY S, AGRAWAL H, BAUER E, FURST DE: odontitis in a patient with chronic cutaneous
ability to set cut-offs for pathogenic anti- Infection and Lupus: which causes which? lupus erythematosus: a case report. Quintes-
bacterial antibody positivity since it is Curr Rheumatol Rep 2016; 18: 13. sence Int 2006; 37: 401-8.
23. FABBRI C, FULLER R, BONFÁ E, GUEDES LK,
possible that the non-SLE controls were 7. RYDER MI: Comparison of neutrophil func-
tions in aggressive and chronic periodontitis. D’ALLEVA PS, BORBA EF: Periodontitis treat-
also exposed to some of these bacteria Periodontol 2000. 2010; 53: 124-37. ment improves systemic lupus erythematosus
(Supplementary Fig. 3). Despite these 8. YEW HS, CHAMBERS ST, ROBERTS SA et al.: response to immunosuppressive therapy. Clin
limitations, our data suggest an associa- Association between HACEK bacteraemia Rheumatol 2014; 33: 505-9.
and endocarditis. J Med Microbiol 2014; 63: 24. KONIG MF, ABUSLEME L, REINHOLDT J et
tion between exposure to specific peri- al.: Aggregatibacter actinomycetemcomitans-
892-5.
odontal pathogens and lupus disease ac- 9. MEYER DH, LIPPMANN JE, FIVES-TAYLOR induced hypercitrullination links periodontal
tivity in SLE patients. Previous studies PM: Invasion of epithelial cells by Actinoba- infection to autoimmunity in rheumatoid ar-
show a higher incidence of periodontal cillus actinomycetemcomitans: a dynamic, thritis. Sci Transl Med 2016; 8: 369ra176.
multistep process. Infect Immun 1996; 64: 25. LAKIO L, ANTINHEIMO J, PAJU S, BUHLIN K,
disease in SLE patients (20, 21). Taken PUSSINEN PJ, ALFTHAN G: Tracking of plasma
2988-97.
together, all these studies confirm the 10. SZYMULA A, ROSENTHAL J, SZCZERBA antibodies against Aggregatibacter actinomy-
interaction between periodontal disease BM, BAGAVANT H, FU SM, DESHMUKH US: cetemcomitans and Porphyromonas gingivalis
and SLE, and specifically, suggest a role T cell epitope mimicry between Sjögren’s during 15 years. J Oral Microbiol 2009; 1.
syndrome Antigen A (SSA)/Ro60 and oral, 26. EBERSOLE JL, CAPPELLI D, STEFFEN MJ:
for gingival bacterial infections as a fac- gut, skin and vaginal bacteria. Clin Immunol Characteristics and utilization of antibody
tor for increasing morbidity in SLE. 2014; 152: 1-9. measurements in clinical studies of periodon-
An interesting clinical study in SLE 11. RUTTER-LOCHER Z, SMITH TO, GILES I, tal disease. J Periodontol 1992; 63: 1110-6.
patients (n=49) showed that aggressive SOFAT N: Association between systemic lupus 27. KURU B, McCULLOUGH MJ, YILMAZ S, POR-
erythematosus and periodontitis: a system- TER SR: Clinical and microbiological studies
treatment of periodontitis resulted in a atic review and meta-analysis. Front Immunol of periodontal disease in Sjögren syndrome
significant improvement in the respons- 2017; 8: 1295. patients. J Clin Periodontol 2002; 29: 92-102.
es to lupus therapy (23). This report 12. CORRÊA JD, CALDERARO DC, FERREIRA GA 28. LUGONJA B, YEO L, MILWARD MR et al.:
et al.: Subgingival microbiota dysbiosis in sys- Periodontitis prevalence and serum antibody
complements our finding of higher lupus
temic lupus erythematosus: association with reactivity to periodontal bacteria in primary
activity in patients with potential expo- periodontal status. Microbiome 2017; 5: 34. Sjögren’s syndrome: a pilot study. J Clin
sure to specific bacteria. Prevention of 13. PAPAPANOU PN, NEIDERUD AM, DISICK E, Periodontol 2016; 43: 26-33.
periodontal disease and management of LALLA E, MILLER GC, DAHLÉN G: Longitu- 29. de GOÉS SOARES L, ROCHA RL, BAGORDA-
dinal stability of serum immunoglobulin G KIS E, GALVÃO EL, DOUGLAS-de-OLIVEI-
periodontal health have been advocated RA DW, FALCI SGM: Relationship between
responses to periodontal bacteria. J Clin Peri-
as simple tools for reducing morbidity in odontol 2004; 31: 985-90. sjögren syndrome and periodontal status: A
debilitating systemic disease states (32). 14. CUNNINGHAM LL, NOVAK MJ, MADSEN M, systematic review. Oral Surg Oral Med Oral
Our study provides support for conduct- ABADI B, EBERSOLE JL: A bidirectional rela- Pathol Oral Radiol 2018; 125: 223-31.
tionship of oral-systemic responses: observa- 30. LE GALL M, CORNEC D, PERS JO et al.: A pro-
ing systematic clinical investigations tions of systemic host responses in patients spective evaluation of dental and periodontal
into periodontal disease in SLE and a after full-mouth extractions. Oral Surg Oral status in patients with suspected Sjögren’s
rationale for aggressive management of Med Oral Pathol Oral Radiol 2014; 117: 435- syndrome. Joint Bone Spine 2016; 83: 235-6.
periodontal health in SLE patients. 44. 31. KONIG MF, ANDRADE F: A critical reappraisal
15. KUDO C, NARUISHI K, MAEDA H et al.: of neutrophil extracellular traps and NETosis
Assessment of the plasma/serum IgG test to mimics based on differential requirements for
Acknowledgements screen for periodontitis. J Dent Res 2012; 91: protein citrullination. Front Immunol 2016; 7:
The assistance from Mr Stan Kamp 1190-5. 461.
16. DYE BA, HERRERA-ABREU M, LERCHE- 32. CULLINAN MP, SEYMOUR GJ: Periodontal
and Ms Louise Williamson in compil-
SEHM J et al.: Serum antibodies to periodon- disease and systemic illness: will the evidence
ing and submitting this manuscript is tal bacteria as diagnostic markers of peri- ever be enough? Periodontol 2000. 2013; 62:
gratefully acknowledged. odontitis. J Periodontol 2009; 80: 634-47. 271-86.
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