Evaluation of Salivary Anti-CCP in Relation to Some Oral Manifestations in Rheumatoid Arthritis Patients, Sulaimaniyah, Iraq

doi:10.21203/rs.3.rs-3147247/v1

Download PDF

Research Article

Evaluation of Salivary Anti-CCP in Relation to Some Oral Manifestations in Rheumatoid Arthritis Patients, Sulaimaniyah, Iraq

https://doi.org/10.21203/rs.3.rs-3147247/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Background

Rheumatoid arthritis (RA) affects the oral cavity, mainly the exocrine salivary gland function causing decreased salivary flow rate.

Objectives

To determine the salivary flow rate, pH, and the main oral manifestations in RA patients. Also, to evaluate the level of antibodies to the cyclic citrullinated peptide (CCP) in the saliva.

Subjects and methods

A matched case-control study was conducted at Rheumatology Centre, Sulaimaniyah, Iraq, on 90 subjects (50 RA patients and 40 healthy controls) from January 2021 to January 2022. The oral cavity was thoroughly examined for signs of oral and temporomandibular joint (TMJ) involvement and to assess the Decayed, Missed, Filled Teeth (DMFT) index and oral health status. Saliva samples were taken from each subject to measure flow rate, pH, and immunological determination of anti-CCP antibodies using ELISA.

Results

Salivary flow rate was substantially reduced in RA patients. The main oral manifestations were oral ulcerations, redness of the tongue, dry/cracked lips, buccal mucosal dryness, taste disturbances, angular cheilitis, and candidiasis. In addition, TMJ involvement and DMFT were also suggestively more in the RA patients. There was no significant difference between both groups regarding oral hygiene index and the level of salivary anti-CCP antibodies.

Conclusions

Patients with RA exhibited decreased salivary flow rate and generally poorer oral health status.

Autoimmune disease

blood biomarker

salivary variables

case-control study

Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune, systemic illness described by inflammation of joints and damage of cartilage/bone with significant consequences for multiple organ involvement that results in oedema, ache, stiffness, and function loss [1]. RA is also characterized by systemic manifestations, including hematologic, neurologic, cardiovascular, and damage of the lacrimal/salivary glands [2].

Additionally, RA accompanies various oral presentations, such as temporomandibular joint (TMJ) ailment, gingivitis, periodontitis, xerostomia, secondary Sjögren’s syndrome, and bacterial/fungal infections. Thus, studies proved that when people with severe RA were treated for oral diseases, some of the RA signs they were experiencing improved and alleviated [3].

Patients with RA usually manifest xerostomia, whereby reduced production and secretion of saliva are seen, which has a detrimental effect on the overall oral condition status of the patients [4]. Consequently, hyposalivation is manifested by furrowed/erythematous tongue, atrophic mucosa, remaining food particles, and cervical caries [5]. TMJ is commonly displayed with pain, masticatory muscle tenderness, sound in the joint, and diminished joint movement [6]. Moreover, oral health issues related to RA and its management/treatments might cause other complications for patients because of their immunosuppressive actions. RA treatments can stimulate candidiasis and oral ulceration assisted by a deficiency of saliva [7].

Commonly used tests for diagnosis of RA includes investigation for the anti-nuclear antibody (ANA), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), and anti-cyclic-citrullinated peptide (CCP) antibodies. RF is a critical serological investigation for diagnosing RA, despite its specificity limitation, as it is not only detected in RA patients but is also noticed in other autoimmune/infectious diseases. More importantly, anti-CCP antibodies are typically formed in RA patients, and these autoantibodies start directing/attacking otherwise healthy tissues. Thus, anti-CCP antibodies are highly suggested for RA, and they reflect particular biomarkers for the diagnosis/prognosis of RA due to their relevant specificity/sensitivity [8, 9].

Therefore, this study was designed to consider the main oral complications affecting patients with RA and present the valuable aspects of RF and anti-CCP antibodies as biomarkers of inflammation using the ELISA technique.

Study design and setting

A case-control study was performed in Rheumatology Centre, Sulaimaniyah, Iraq, on 50 patients with established RA of both genders (6 males and 44 females) and 40 healthy adults (4 males and 36 females) who were age and sex-matched to the RA group, from January 2021 to January 2022.

Questionnaire

A validated, self-prepared questionnaire was designed to include patients’ socio-demographic characteristics (gender and age), occupation, smoking status, information on the medication used, and oral complaints, especially dry mouth.

Study protocol

An extensive clinical investigation of the oral mucosa was done for any signs of oral ulceration, redness, and dryness [10] . Then, to determine the dry mouth sensation (xerostomia/ salivary gland hypofunction), a score of 0 was given to patients who practised no feeling of dry mouth, a score of 1 was given to patients that had a slight feeling of dry mouth, a score of 2 was given to those that had a pronounced feeling of dry mouth, and score 3 was allocated to those with a severe feeling of dry mouth that creates difficult speech (score 3) [11] . Additionally, salivary flow rate and pH were determined following the standard procedure [12] .

To assess TMJ involvement, sound over TMJ, click, crepitus, tenderness over TMJ, tenderness over masticatory muscle, pain during jaw opening, maximal mouth opening (interincisal distance of <40 mm), deviation of the mandible was reported [13] . The dental status of subjects was found using the DMFT index, while oral hygiene was assessed using the oral hygiene index-simplified (OHI-S).

A human anti-CCP antibody ELISA kit (Elabscience®, USA) was used to determine salivary IgA anti-CCP through the Sandwich method. Briefly, the micro-plate was pre-coated with antigen, standards/samples were added, and then a biotinylated detection antigen specific for anti-CCP antibody/Vidin-Horseradish Peroxidase (HRP) conjugate was added and incubated. Later on, free components were washed off, and the substrate solution was added. Wells that had anti-CCP antibodies became blue. Then, the enzyme-substrate reaction was completed by adding sulphuric acid, and the colour became yellow. The optical density (OD) proportional to the concentration of anti-CCP antibody was measured spectrophotometrically at a wavelength of 450±2 nm, and the standard curve was determined (Figure 1).

Statistical analysis

Statistical Package for the Social Sciences (SPSS, version 25) was used for data analysis. The significant difference between groups in respect of different quantitative variables was assessed using the independent t-test. The chi-square test was used to compare the categorical data between groups. Linear regression showed the association between DMFT and salivary flow rate. A p-value of <0.05 was considered a significant correlation, while <0.001 was highly significant.

Participants’ socio-demographic features

Most participants were females in both groups (44 among cases and 37 among controls). The mean patient’s age of the RA group was 48.04 ± 13.07 (ranging from 25–76 years), while it was 42.93 ± 9.21 (ranging from 25–66 years) in the control group. Regarding the occupation, most patients in RA group (72%) and 38% in control group were housewives. Also, most patients in both groups were nonsmokers (86% in RA group and 74% in control group), while only 2% was x-smoker in both groups, others were smokers. The highest frequency of the drugs used by the RA patients was methotrexate (72%), followed by prednisolone (18%), and 12% used other drugs such as hydroxychloroquine and sulfasalazine.

Salivary flow rate and salivary pH

The mean salivary flow rate and pH in the RA group were significantly (p < 0.05) lower than the healthy control group (Table 1).

Table 1

Salivary flow rate and pH of studied groups.
Variable		RA Patients	Control	P-value
Salivary flow rate	Mean ± SD	0.20 ± 0.11	0.29 ± 0.17	< 0.01*
	Median	0.20	0.40
	Range	0.49	0.70
	Interquartile range	0.14	0.20
	Mean Rank	36.8	51.20	0.01*
Salivary pH	Mean ± SD	6.39 ± 0.49	6.63 ± 0.33	0.01*
Total		50	40
RA: Rheumatoid arthritis, *: Significant difference

Subjects’ feeling of oral dryness

There was a significant difference (p < 0.05) in the feeling of oral dryness between the RA and control groups. Patients with RA experienced more severe dry mouth difficulties, and their oral functions were more compromised than healthy controls (Fig. 2).

Oral manifestation findings

There was a significant (p < 0.05) increase in the level of oral manifestation in the RA group compared to healthy controls. Oral examination revealed that 34% of the patients had taste disturbances,16% had salivary gland enlargement, 30% had angular cheilitis, 24% had intra-oral candidiasis, 38% had cracked and dry lips, 76% had buccal mucosal dryness, 44% had tongue redness, and 42% had mouth ulcers (Table 2).

Table 2

Oral manifestations of studied groups.
Oral manifestation	RA Patients	Control	P-value
Oral manifestation	Number; %
Buccal mucosa paleness	38 (76)	0 (0.0)	0.001**
Tongue redness	22 (44)	0 (0.0)	0.001**
Mouth ulcer	21 (42)	0 (0.0)	< 0.001*
Lip cracking	19 (38)	0 (0.0)	0.001**
Taste disturbance	17 (34)	0 (0.0)	< 0.001*
Angular cheilitis	15 (30)	1 (2.5)	0.001**
Candidiasis	12 (24)	1 (2.5)	0.003**
Salivary gland enlargement	8 (16)	0 (0.0)	0.01*
Total	50	40
RA: Rheumatoid arthritis, : Significant difference, *: Highly significant difference

DMFT and oral hygiene indices

The DMFT index was significantly higher in the RA group than in the control group (p = 0.04), especially the missing and decayed teeth index. In the RA group, 24% were completely edentulous, and 6% were partially edentulous. In the control group, 12.5% were completely edentulous, and 10% were partly edentulous (Table 3). Regarding the oral hygiene index, there was a significant difference (p = 0.001) for the debris index without a substantial difference (p = 0.51) for the calculus index between both groups (Table 4).

Table 3

DMFT index in studied groups.
DMFT	RA Patients	Control	P-value
Decayed teeth	5.14 ± 3.66	2.61 ± 1.84	0.001**
Missing teeth	7.86 ± 5.61	3.81 ± 2.32	< 0.001
Filled teeth	2.83 ± 3.18	3.39 ± 2.77	0.45
DMF teeth	11.08 ± 8.55	7.79 ± 5.27	0.04*
Complete edentulous	12 (24.0%)	5 (12.5%)	0.20
Partial edentulous	3 (6.0%)	4 (10.0%)
Total	35	31
DMFT: Decayed, Missed, Filled Teeth; RA: Rheumatoid arthritis, : Significant difference, *: Highly significant difference

Table 4

Oral hygiene index in studied groups.
Oral hygiene	RA Patients	Control	P-value
Oral hygiene	Mean ± SD		P-value
Debris index	0.46 ± 0.51	0.12 ± 0.22	0.001**
Calculus index	0.56 ± 0.49	0.49 ± 0.37	0.51
Oral hygiene index	0.76 ± 0.85	0.51 ± 0.54	0.12
RA: Rheumatoid arthritis, **: Highly significant difference

TMJ clinical findings

The symptomatic features of TMJ problems were significantly higher in the RA group than in healthy controls, including TMJ click (p = 0.002), TMJ tenderness (p = 0.02), masticatory tenderness (p = 0.03), and pain on mouth opening (p = 0.003) (Table 5).

Table 5

TMJ clinical findings in studied groups.
TMJ findings	RA Patients	Control	P-value
TMJ findings	Number; %		P-value
TMJ click	23 (46)	6 (15)	0.002**
TMJ crepitus	3 (6)	0 (0.0)	0.12
TMJ tenderness	15 (30)	4 (10.0)	0.02*
Masticatory tenderness	22 (44)	9 (22.5)	0.03*
Pain on mouth opening	10 (20)	0 (0.0)	0.003**
Maximal mouth opening	50 (100)	40 (100)	1.0
Deviation of mandible	2 (4)	0 (0.0)	0.20
RA: Rheumatoid arthritis, : Significant difference, *: Highly significant difference

Estimation of salivary anti-CCP antibodies

No significant difference (p = 0.85) was found for salivary anti-CCP between both groups (Fig. 3).

Correlation between salivary flow rate and feeling of oral dryness

A significant positive correlation existed between salivary flow rate and feeling of oral dryness (p < 0.001). Patients with decreased salivary flow rate also experienced more difficulty feeling oral dryness (Table 6).

Table 6

Correlation between salivary flow rate and feeling of oral dryness in studied groups.
Oral dryness symptom	Salivary flow rate		P-value
Oral dryness symptom	Number	Mean ± SD	P-value
No feeling	39	0.32 ± 0.16	< 0.001**
Slight feeling	27	0.19 ± 0.11
Pronounced feeling	18	0.16 ± 0.08
Severe feeling	2.0	0.03 ± 0.03
**: Highly significant difference

Correlation between salivary flow rate and oral manifestations

There was an insignificant correlation between the salivary flow rate and oral presentations except for buccal mucosal dryness (p = 0.005) and tongue disturbance (p = 0.01) (Table 7).

Table 7

Correlation between salivary flow rate and oral manifestations in studied groups.
Oral manifestation		Salivary flow rate		P-value
Oral manifestation		Number	Mean ± SD	P-value
Taste disturbance	Yes	14	0.17 ± 0.09	0.06
Taste disturbance	No	72	0.26 ± 0.15	0.06
Salivary gland enlargement	Yes	7	0.16 ± 0.05	0.15
Salivary gland enlargement	No	79	0.25 ± 0.15	0.15
Angular cheilitis	Yes	13	0.18 ± 0.11	0.12
Angular cheilitis	No	72	0.25 ± 0.15	0.12
Candidiasis	Yes	10	0.18 ± 0.14	0.16
Candidiasis	No	75	0.25 ± 0.15	0.16
Lip cracking	Normal	69	0.26 ± 0.15	0.06
Lip cracking	Abnormal	17	0.18 ± 0.12	0.06
Buccal mucosa paleness	Normal	51	0.28 ± 0.16	0.005**
Buccal mucosa paleness	Abnormal	35	0.19 ± 0.10	0.005**
Tongue redness	Yes	18	0.16 ± 0.11	0.01*
Tongue redness	No	68	0.26 ± 0.15	0.01*
Mouth ulcer	Yes	20	0.19 ± 0.13	0.07
Mouth ulcer	No	66	0.26 ± 0.15	0.07
: Significant difference, *: Highly significant difference

Correlation between salivary flow rate and DMFT index

The DMFT score was inversely correlated to the salivary flow rate (p = 0.02) (Table 8).

Table 8

Correlation between salivary flow rate and DMFT index.
Salivary flow rate (ml/min)	DMFT				P-value
	B Coefficients	95% CI for B	R	R²
	-0.008	(− 0.015 to − 0.001)	0.279	0.078	0.02*
DMFT: Decayed, Missed, Filled Teeth, *: Significant difference

From the results of this study, it's evident that women were much more liable to be affected by the disease than men of the same age, following the findings of Pederson et al. 2006 [14], who suggested that sex hormones might be involved in RA. Additionally, the result has revealed a significant decrease in salivary fluid secretion in the RA group to the control group, in which four patients were xerostomic (no saliva secretion at all); this could be attributed to secondary Sjögren syndrome. In this regard, Zalewska et al. 2013 [2] found xerostomia in RA patients followed by a substantial decrease in salivary flow in the control group. It was also agreed with the outcomes of some other studies [3, 15, 16].

Regarding salivary pH, the current study revealed a significant difference (p = 0.01) in salivary pH between the two studied groups. The mean pH value in the control group was 6.63, while in the study group, it was 6.39. These outcomes confirm that when the physiological salivary pH range increases, the flow rate of saliva increases and vice versa. This finding was compatible with that reported by Bardow et al. 2000 [17], who concluded that saliva pH became significantly more alkaline with increasing flow rates. However, it’s contrary to the results of Farsi, 2007 [18], who found no significant changes in pH in salivary flow rate.

The general feeling of oral dryness was higher among the RA group. Regarding xerostomia about oral function, in a possible sum score of 0–4, most patients reported sipping liquid to aid in swallowing dry foods, and many reported having no problem-consuming dry food. At the same time, none of the subjects answered if the saliva in their mouth seemed too little or too much. These results agreed with Uhlig et al. 1999 [19], who demonstrated a high occurrence of oral dryness in RA patients.

For the oral manifestations that could be observed in RA, we demonstrated a significant increase among the RA group compared to the healthy controls, especially taste disturbance (34%) and mouth ulcer (42%). Although one subject in the control group had angular cheilitis and another had oral candidiasis, this could be attributed to inadequate oral hygiene. These outcomes follow that of Al-Yassin, 2013 [20], who found oral ulceration to be the most prominent manifestation in RA patients.

Moreover, our finding has proved identical or very similar to those found by Zalewska et al. 2011 [21], who confirmed that the DMFT index was 1.229 times higher in RA than in healthy controls. Likewise, Zalewska et al. 2013 [2] reported a significantly higher DMFT index in the RA group than in healthy controls. However, Yamakawa et al. 2002 [22] found no significant difference in the number of decayed or filled teeth between the two groups but significantly found more missing teeth in the RA group. Thus DMFTs were substantially more numerous overall. On the other hand, Silvister-Rangil et al. 2016 [3], and Pischon et al. 2008 [23] disagree with our finding, as they could not establish a significant difference in the DMFT index between the two groups. However, the result showed that the percentages of subjects who were utterly edentulous were higher among the study group, although the difference was insignificant, while the rates of those who were partially edentulous were higher among the control group. These findings are incompatible with those of Yamakawa et al. 2002 [22], who reported significantly higher percentages of partial and complete edentulism among the RA group than the healthy control group.

In this study, there was a significantly higher debris index in the RA group, which could be attributed to the limitation in manual dexterity. However, no significant difference between the groups was found in the calculus index. Thus, OHI-S was insignificant overall. These findings are per Madikeri, 2006 [24], who found no substantial difference in OHI-S between RA and the control group—regarding clinical results in TMJ, patients with RA had significantly more clinical signs and symptoms of TMJ. The joint sound was reported to be the most frequent symptom in RA patients, and this agreed with that of Aliko et al. 2011 [6], Garib and Qaradaxi, 2011 [25], and Abdulla et al. 2014 [26], who found the most frequent TMJ findings in RA were sounding. In the present study, 46% of the patients were presented with TMJ clicks.

In comparison, only 6% had crepitus; this might be ascribed to the fact that most of the patients had medical treatment such as corticosteroid or disease-modifying antirheumatic drugs, which cause less crepitation as the drugs can reduce or prevent damage to the joint [27]. This result was per that reported by Aliko et al. 2011 [6], who found that sounds were mainly presented as clicking, while the occurrence of crepitation on clinical examination was 14%. Meanwhile, these contrasted with other studies [22, 28], which observed a higher frequency of crepitus sound in the TMJ area in RA patients (36% and 29.5%, respectively).

This study also revealed that tenderness in TMJ and the masticatory muscles was significantly higher in the RA group compared to healthy controls, which supports the study by Moen et al., 2005 [10], who found a higher frequency of symptoms and dysfunction related to the TMJ and masticatory system in RA. It’s also compatible with the study by Yamakawa et al. 2002 [22], who reported a more frequent TMJ tenderness in subjects with RA than in non-RA control groups. Moreover, pain during mouth opening was found in the present study to be significantly higher in the RA group, which disagrees with Yamakawa et al. 2002 [22], who observed no differences between the two groups regarding pain. It's also incompatible with that of Pischon et al. 2008 [23], who reported no significant difference in TMJ symptoms between the RA and healthy controls.

Furthermore, both groups had a significant positive correlation between the salivary flow rate and the subjective feeling of oral dryness. This result is compatible with that of Suh et al., 2007 [29] and Márton et al., 2008 [30], who found a strong association between the grade of dry mouth feeling and the unstimulated whole salivary (UWS) flow rates. On the other hand, Hay et al., 1998 [31] and Uhlig et al., 1999 [19] found only a weak association between self-reported symptoms of dry mouth with objective measures of salivary gland function.

Additionally, the correlation of salivary flow rate with oral mucosal changes failed to reach a significant level except for buccal and tongue changes. This might be explained by factors other than saliva help in maintaining mucosal integrity, such as normal secretion from minor salivary glands. However, Kaplan et al., 2008 [32] confirmed a higher frequency of mucosal changes in patients with measurable salivary gland hypofunction. The correlation between the salivary flow rate and the DMFT index was per that reported by Pederson et al., 2005 [33]; we found that the DMFT score is inversely correlated to the salivary flow rate. Besides, Bergdahl, 2000 [34] found an association between the number of teeth and stimulated salivary flow rate. However, Zalewska et al., 2011 [21] could not find any correlation between the salivary flow rate and the DMFT index.

Regarding salivary anti-CCP, our results revealed a deficient level of salivary anti-CCP without a significant difference between RA and the control group which is similar to another study [35]. Also, it was found the presence of salivary IgA did not differ significantly between patients with/without IgA anti-CCP in serum, and this supports the notion that salivary IgA is essentially derived from salivary gland plasma cells, and does not reflect systemic compartment [36]. Hence, the possible leakage from the circulation is of minor importance.

Nevertheless, Kidhir and Al-Jubouri, 2013 reported the mean concentration of salivary anti-CCP in the RA group to be significantly higher than in the healthy control. Also, a positive correlation existed between serum and saliva anti-CCP concentrations in chronic RA patients [37]. One possible reason for these negative results might be explained by the fact that in our research, we applied a kit for the analysis of salivary anti-CCP (Elabscience®), which was designed for research purposes only; this ELISA kit used Sandwich-ELISA as the method, while in other studies salivary IgA was analyzed by modified anti-CCP2 kit, as well as using polyclonal rabbit IgG anti-human α-chain antibodies conjugated with HRP as a secondary antibody [35, 36].

Rheumatoid arthritis is a disease that negatively impacts oral health, predominantly causing decreased salivary flow rate, which in turn causes many oral discomforts. A significant proportion of patients suffering from RA also exhibit signs and symptoms of TMJ involvement. Therefore, it’s predominantly necessary for oral healthcare professionals to recognize and diagnose the oral manifestations related to RA.

Ethics approval and consent to participate

The Ethics Committee of the College of Dentistry, University of Sulaimani, Sulaimaniyah, Iraq, approved the study protocol (No. 56/02-10-2020-UoS). The Declaration of Helsinki performed all experiments. Informed consent was obtained from all subjects, and tooth samples were collected from patients who applied for dental extraction in the hospitals.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no conflict of interest.

Acknowledgements

The authors sincerely acknowledge the Rheumatology Center and College of Dentistry at the University of Sulaimani, Sulaimaniyah, Iraq, for supporting this study project; and offering laboratory facilities.

Authors’ contributions

HNMF: Conceptualization, data collection, data analysis and interpretation, study administration, and original manuscript writing. KMA: Study registration, validation, revision, correction, and edition of the original manuscript. Both authors read and approved the final manuscript before submission.

Funding

This research received no specific grant from any funding agency in the public, commercial, or profit sectors.

Availability of data and materials

The datasets used and analyzed during the current study are available from the corresponding author upon reasonable request.

Ediz L, Hiz O, Ozkol H, Gulcu E, Toprak M, Ceylan MF. Relationship between anti-CCP antibodies and oxidant and anti-oxidant activity in patients with rheumatoid arthritis. Int J Med Sci. 2011;8:139–47.
Zalewska A, Knaś M, Waszkiewicz N, Waszkiel D, Sierakowski S, Zwierz K. Rheumatoid arthritis patients with xerostomia have reduced production of key salivary constituents. Oral Surg Oral Med. 2013;115:483–90.
Silvestre-Rangil J, Bagán L, Silvestre FJ, Bagán JV. Oral manifestations of rheumatoid arthritis. A cross-sectional study of 73 patients. Clin Oral Investig. 2016;20:2575–80.
Vineet R, Nayak M. Sialometric and sialochemical analysis in rheumatoid arthritis patient: a case report. Eur J Biomed Pharm Sci. 2015;2:608–19.
Osailan S, Pramanik R, Shirlaw P, Proctor G, Challacombe S. Clinical assessment of oral dryness: development of a scoring system related to salivary flow and mucosal wetness. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012;114:597–603.
Aliko A, Ciancaglini R, Alushi A, Tafaj A, Ruci D. Temporomandibular joint involvement in rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis. Int J Oral Maxillofac Surg. 2011;40:704–9.
de Souza S, Bansal R, Galloway J. Rheumatoid arthritis–an update for general dental practitioners. Br Dent J. 2016;221:667–73.
van der Helm A, Verpoort FC, Breedveld RE, Toes, Huizinga TW. Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis. Arthritis Res therapy. 2005;7:1–10.
Dionello CF, Rosa Utiyama SR, Radominski SC, Stahlke E, Stinghen ST, de Messias-Reason IJ. Evaluation of rheumatoid factor and anti‐citrullinated peptide antibodies in relation to rheumatological manifestations in patients with leprosy from Southern Brazil. Int J Rheum Dis. 2016;19:1024–31.
Moen K, Bertelsen L, Hellem S, Jonsson R, Brun J. Salivary gland and temporomandibular joint involvement in rheumatoid arthritis: relation to disease activity. Oral Dis. 2005;11:27–34.
Lingjaerde O, Ahlfors U, Bech P, Dencker S, Elgen K. "The UKU side effect rating scale: a new comprehensive rating scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients," Acta Psychiatr Scand Suppl, vol. 76, 1987.
Mahesh D, Komali G, Jayanthi K, Dinesh D, Saikavitha T, Dinesh P. Evaluation of salivary flow rate, pH and buffer in pre, post & post menopausal women on HRT. J Clin Diagn Res. 2014;8:233–6.
Dowrkin S. Research diagnostic criteria for temporomandibular disorders: review, criteria, examinations and specifications, critique. J Craniomandib Disord. 1992;6:301–55.
Pedersen M, Jacobsen S, Klarlund M, Pedersen BV, Wiik A, Wohlfahrt J, et al. Environmental risk factors differ between rheumatoid arthritis with and without auto-antibodies against cyclic citrullinated peptides. Arthritis Res Ther. 2006;8:1–15.
Nagler R, Salameh F, Reznick A, Livshits V, Nahir A. "Salivary gland involvement in rheumatoid arthritis and its relationship to induced oxidative stress," Rheumatology, vol. 42, pp. 1234–1241, 2003.
Aliko A, Ciancaglini R, Alushi A, Tafaj A. Sicca symptoms, and lacrimal and salivary flow in Albanian patients with rheumatoid arthritis. J Oral Pathol Med. 2010;39:651–6.
Bardow A, Moe D, Nyvad B, Nauntofte B. The buffer capacity and buffer systems of human whole saliva measured without loss of CO2. Arch Oral Biol. 2000;45:1–12.
Farsi NM. Signs of oral dryness in relation to salivary flow rate, pH, buffering capacity and dry mouth complaints. BMC Oral Health. 2007;7:1–6.
Uhlig T, Kvien TK, Jensen JL, Axéll T. Sicca symptoms, saliva and tear production, and disease variables in 636 patients with rheumatoid arthritis. Ann Rheum Dis. 1999;58:415–22.
Al-yassiri AMH. "Oral Find Rheumatoid Arthritis Patients " Karbala J med, vol. 6, 2013.
Zalewska A, Waszkiewicz N, Szajda SD, Waszkiel D. "Impact of salivary flow and lysozyme content and output on the oral health of rheumatoid arthritis patients," Postepy Hig Med Dosw (online), vol. 65, pp. 40–45, 2011.
Yamakawa M, Ansai T, Kasai S, Ohmaru T, Takeuchi H, Kawaguchi T et al. ,., "Dentition status and temporomandibular joint disorders in patients with rheumatoid arthritis," Cranio, vol. 20, pp. 165–171, 2002.
Pischon N, Pischon T, Kröger J, Gülmez E, Kleber BM, Bernimoulin JP, et al. Association among rheumatoid arthritis, oral hygiene, and periodontitis. J Periodontol. 2008;79:979–86.
Madikeri R. "Relationship between rheumatoid arthiritis and chronic periodontitis," RGUHS, 2006.
Garib BT, Qaradaxi SS. Temporomandibular joint problems and periodontal condition in rheumatoid arthritis patients in relation to their rheumatologic status. J Oral Maxillofac Surg. 2011;69:2971–8.
Abdulla HI, Kubba AN, Al-khalissy MM. Evaluation of The Effects Of Rheumatoid Arthritis On The Hard And Soft Tissue Components Of The Temporomandibular Joint By Using Magnetic Resonance Imaging. Iraqi Dent J. 2014;36:25–9.
Sidebottom A, Salha R. Management of the temporomandibular joint in rheumatoid disorders. Br J Oral Maxillofac Surg. 2013;51:191–8.
Bessa-Nogueira RV, do Egito Vasconcelos BC, Duarte AP, Góes PS, Bezerra TP. Targeted assessment of the temporomandibular joint in patients with rheumatoid arthritis. J Oral Maxillofac Surg. 2008;66:1804–11.
Suh KI, Lee JY, Chung JW, Kim YK, Kho HS. Relationship between salivary flow rate and clinical symptoms and behaviours in patients with dry mouth. J Oral Rehabil. 2007;34:739–44.
Márton K, Madléna M, Bánóczy J, Varga G, Fejérdy P, Sreebny L, et al. Unstimulated whole saliva flow rate in relation to sicca symptoms in Hungary. Oral Dis. 2008;14:472–7.
Hay EM, Thomas E, Pal B, Hajeer A, Chambers H, Silman A. Weak association between subjective symptoms of and objective testing for dry eyes and dry mouth: results from a population based study. Ann Rheum Dis. 1998;57:20–4.
Kaplan I, Zuk-Paz L, Wolff A. Association between salivary flow rates, oral symptoms, and oral mucosal status. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008;106:235–41.
Pedersen AML, Bardow A, Nauntofte B. Salivary changes and dental caries as potential oral markers of autoimmune salivary gland dysfunction in primary Sjögren's syndrome. BMC Clin Pathol. 2005;5:1–13.
Bergdahl M. Salivary flow and oral complaints in adult dental patients. Community Dent Oral Epidemiol. 2000;28:59–66.
Svärd A, Kastbom A, Sommarin Y, Skogh T. "Salivary IgA antibodies to cyclic citrullinated peptides (CCP) in rheumatoid arthritis," Immunobiology, vol. 218, pp. 232–237, 2013.
Svärd A. Circulating and Mucosal Antibodies to Citrullinated Antigens in Rheumatoid Arthritis. Linköping University Electronic Press; 2014.
Khidhir RM, Al-Jubouri RH. The study of tempromandibular joint disorders and anti-cyclic citrullinated peptide antibodies in serum and saliva of patients with rheumatoid arthritis. J Baghdad Coll Dentistry. 2013;25:67–71.

No competing interests reported.

Download PDF

Version 1

posted

You are reading this latest preprint version

Evaluation of Salivary Anti-CCP in Relation to Some Oral Manifestations in Rheumatoid Arthritis Patients, Sulaimaniyah, Iraq

Status:

Version 1

Abstract

Figures

Introduction

Subjects and Methods

Results

Participants’ socio-demographic features

Salivary flow rate and salivary pH

Subjects’ feeling of oral dryness

Oral manifestation findings

DMFT and oral hygiene indices

TMJ clinical findings

Estimation of salivary anti-CCP antibodies

Correlation between salivary flow rate and feeling of oral dryness

Correlation between salivary flow rate and oral manifestations

Correlation between salivary flow rate and DMFT index

Discussion

Conclusions

Declarations

References

Additional Declarations

Status:

Version 1