|Year : 2019 | Volume
| Issue : 1 | Page : 24-28
Role of immunological alterations in oral submucous fibrosis
Sarada Malempati1, Vamshi Krishna Guttikonda2, Thejasri Vishnubhatla2, Mahesh Neerupakam2, Sridevi Koduri2, Krishnaveni Buduru2
1 Department of Oral Medicine and Radiology, GSL Dental College, Rajahmundry, Andhra Pradesh, India
2 Department of Oral Medicine and Radiology, Lenora Institute of Dental Sciences, Rajahmundry, Andhra Pradesh, India
|Date of Submission||27-Oct-2018|
|Date of Acceptance||28-Feb-2019|
|Date of Web Publication||23-Apr-2019|
Dr. Sarada Malempati
Department of Oral Medicine and Radiology, GSL Dental College, Rajahmundry - 533 294, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Oral Submucous fibrosis (OSMF) is a premalignant condition affecting the oral mucosa. It is observed to have a multifactorial etiology including genetic predisposition and autoimmune origin. This study aimed to study the etiological role of immunological factors in OSMF. Settings and Design: It was a prospective study carried out in the Department of Oral Medicine and Radiology at Lenora Institute of Dental Sciences, Rajahmundry. Aims and Objective: To estimate and compare the serum IgG and IgA between the OSMF subjects and controls. To assess the statistical significance of the difference in the levels of albumin, globulin, total protein, IgG and IgA between study group and control group if any. Materials and Methods: It was an observational study in which the serum albumin, serum globulin, total protein, IgG and IgA were evaluated in a total of 60 patients who gave consent to participate in the study. Results and Discussion: Increase of IgG was observed in 9 (30%) subjects of the OSMF group and in 4 (13.2%) of the control group. IgA level was increased in 2 (6.6%) subjects of OSMF group and in 5 (16.6%) subjects of the control group. However, this difference was not statistically significant. Conclusion: The findings from the study indicated an alteration in the immunoglobulin level in patients with OSMF. However, the association was not significant. Therefore, further and larger studies are advocated to verify the immunological association with OSMF. One important observation made in the study was a positive association between the duration of exposure and stage of OSMF. This implies that interventions which modify the arecanut chewing habits can bring about a reduction in OSMF and in turn oral cancer.
Keywords: Arecanut, IgA, IgG, immunoglobulin, oral submucous fibrosis
|How to cite this article:|
Malempati S, Guttikonda VK, Vishnubhatla T, Neerupakam M, Koduri S, Buduru K. Role of immunological alterations in oral submucous fibrosis. J Indian Acad Oral Med Radiol 2019;31:24-8
|How to cite this URL:|
Malempati S, Guttikonda VK, Vishnubhatla T, Neerupakam M, Koduri S, Buduru K. Role of immunological alterations in oral submucous fibrosis. J Indian Acad Oral Med Radiol [serial online] 2019 [cited 2020 Jan 28];31:24-8. Available from: http://www.jiaomr.in/text.asp?2019/31/1/24/256894
| Introduction|| |
Oral Submucous fibrosis (OSMF) is a premalignant condition that affects the oral mucosa and is linked to arecanut (betel nut) chewing. It is predominantly seen in Southeast Asians but off late is found among Europeans and North Americans. It can cause morbidity status post-transformation into squamous cell carcinoma (SCC). OSMF has been described as early as 2500–3000 B.C. by Sushrutha in his ancient book as “vidari” a condition which resembles OSMF. Schwartz in 1952 described it as atrophic idiopathic mucosa oris. It was given the term oral submucous fibrosis by Joshi in 1953.
OSMF initially starts as oral mucosal stiffness that may lead to trismus and difficulty while eating. Clinically it might present as difficulty in mouth opening, tongue protrusion, difficulty in phonetics, and deglutition.
Consumption of arecanut is believed to be one of the important causes of OSMF. However, the exact etiology is still obscure. Intake of other irritants such as capsaicin in chilies, vitamin deficiency, and streptococcal infection are also believed to play a role in OSMF. OSMF was found to show changes similar to that seen in collagen disorders such as rheumatoid arthritis and scleroderma, etc., This was further supported by the fact that alkaloids and tannins present in arecanut have the potential to increase the collagen activity. However, the one draw-back of this theory is that the presence of lupus erythematosus (LE) cells has not been shown in OSMF.
The pathological changes in OSMF are, an initial juxtaepithelial inflammatory reaction followed by fibroelastic changes in the submucosa and epithelial atrophy manifesting as the stiffness of the oral mucosa and trismus.
OSMF has also been shown to have a genetic predisposition and has been shown to be associated with HLA A110, DR3, DR7, and probably B7. Considering that OSMF is seen in patients without exposure to irritants and the consistent association with hyperglobulinemia suggests an immunological mechanism of origin. However, an analysis of the various subfractions of Immunoglobulin's did not reveal a consistent pattern. OSMF, therefore, appears to have a multifactorial etiology.
There is several literature evidence which supports the immunological association of OSMF. Pathak et al. were one of the initial studies that favored the autoimmune hypothesis of OSMF. In their study, it was seen that patients with OSMF had increased levels of IgG. Considering the immunological association of disease, this study estimated serum proteins and immunoglobulins (IgG and IgA) levels in patients with OSMF and examined if changes were consistent. A study by Rajendran et al. (1986), showed that levels of serum IgA, IgD, and IgE were found to be elevated both in OSMF and oral cancer. Similarly, P Ramani et al. (1988), indicated that circulating immune complexes and their immunoglobulin contents were significantly elevated in patients with oral submucous fibrosis and in patients with oral cancer. Naseem Shah et al. (1994), S Anil et al. (1995), Pinakapani et al. (2009), N J Mary et al. (2016), Prajapati et al. (2016), Kandaswamy et al. (2016), Balakrishna C et al. (2015) were some of the other studies that showed that OSMF was associated with immunoglobulin elevation.,,,,,, However few of the other by Scully CS (1981/82) and Divya V C et al. (2014) showed conflicting results., These studies also did not show conclusive evidence on the association between serum albumin levels and OSMF.
The present study was planned to estimate serum total protein, albumin, globulin, and immunoglobulins IgG and IgA in 30 OSMF patients and 30 age and gender-matched controls.
| Materials and Methods|| |
This observational study conducted in the department of Oral Medicine and Radiology, Lenora Institute of Dental Sciences, after obtaining ethical clearance for the study. A total of 30 subjects diagnosed with OSMF and 30 age and gender-matched controls were included in the study. The study subjects were chosen from those attending the Out Patient Department of Oral Medicine and Radiology, Lenora Institute of Dental Sciences, Rajanagaram, East Godavari district, Andhra Pradesh.
Subjects willing to participate in the study were explained about the study in the language known to them and an informed consent was obtained.
The objectives of the study were:
- To estimate serum albumin and total protein in OSMF subjects and controls.
- To estimate and compare serum IgG, IgA between OSMF subjects and controls.
- To assess the statistical significance of the data obtained from the study group and the control group.
The recruited subjects were made to sit comfortably on a dental chair with artificial illumination. Demographic data [Table 1] and thorough case history were recorded for OSMF group and control group. Maximum mouth opening was measured and recorded with a divider and vernier caliper.
Patients with OSMF were classified according to the criteria established by J.J. Pindborg in the year 1989 into 3 clinical stages [Table 2].
Stage 1: Stomatitis includes erythematous mucosa, vesicles, mucosal ulcers, melanotic mucosal pigmentation, and mucosal petechiae.
Stage 2: Fibrosis occurs in ruptured vesicles and ulcers when they heal.
Stage 3: Fibrosis along with any of the following sequel such as speech and hearing defects, or presence of other potentially malignant disorders such as leukoplakia and malignancy.
Venous blood, 5 mL was drawn from the right median cubital vein of all the subjects via venipuncture. This was used for analyzing the serum albumin, globulin, total protein, IgA and IgG.
| Results|| |
The findings of the study were analyzed and showed the following results:
Total protein in the OSMF group was within a range of 93.3%, and increased in 6.6% of the subjects; total protein in the control group was within a range of 90% of the subjects and increased in 9.9% of the subjects [Graph 1].
Albumin values were observed to be within range for both OSMF as well as a control group [Graph 2].
Globulin levels were within in range of 90% and increased in 9.95 of subjects with OSMF; was within a range of 93.3% and increased in 6.6% of subjects in the control group [Graph 3] and [Table 3].
|Table 3: Population percentage with total protein, albumin and globulin ranges in group A and B|
Click here to view
IgG range of OSMF group was, 9.3-18.0 g/l and that of the control group was 9.7-16.9 g/l, mean and standard deviation of 14.578 ± 2.72 g/L and 14.053 ± 2.041 g/L, respectively. [Graph 4]. IgA of OSMF group ranged from 1.0-6.2 g/l and that of the control group was from 1.3 to 5.3 g/l, mean and standard deviation of 2.522 ± 1.15 g/l and 2.893 ± 1.05 g/l, respectively. The ranges of IgG and IgA and mean and standard deviation of IgG showed a marginal increase in group A when compared to group B. Mean and standard deviation of IgA was less in group A when compared to group B with the P value of 0.403 and 0.201, respectively [Graph 5] and [Table 4].
|Table 4: Range and mean and standard deviation of IgG, IgA and total immunoglobulins in group A and B|
Click here to view
An increase of IgG was observed in 9 (30%) subjects of the OSMF group and in 4 (13.2%) control group. IgA level was increased in 2 (6.6%) subjects of OSMF group and in 5 (16.6%) subjects of the control group. However, this difference was not statistically significant [Table 5].
One other important observation made was that there was a positive correlation between clinical stage and habit duration [Table 6].
| Discussion|| |
The findings in our study were in line with the observation in other studies described in the literature. Our study showed a male preponderance (73%), with patients aged between 20 and 40 years (mean of 34.6 ± 12.42 years). These results were in accordance with previous studies done by K.S. Ganapathy et al. (80% males, mean age 28.8 ± 8.34 years); Zameera A et al. (92% male, mean age 27.3 ± 7.8 years), and Patidar et al. (83.3%, mean age 32.03 ± 9.644). [Table 1] It was observed that in the current study most of the affected were the younger population of lower socioeconomic status which is in line with findings from literature resources and is attributed to the economic independence and experimental attitude of the people of that age.
Majority of the study population (86.6%) were in stage II having habit duration of 11–20 years. Approximately, 6.6% of the patients were in stage I and III with a habit duration of 1–10 and 21–30 years. There was positive correlation with duration of habit and clinical stage which was statistically significant (Pearson correlation test). This observation is in accordance with Kandasamy et al. where 60% of patients with habit duration of more than 5 years developed OSMF.
Similar to the Balakrishnan et al. study, the total protein was found to be marginally reduced in patients with OSMF when compared with the controls. Various studies have found a positive correlation between Ig levels to total serum protein where the latter was shown to drop significantly in OSMF patients. However, in our study although there was reduction, the difference was not statistically significant. This observation was at variance with finding from Anuradha CD et al. and Zameera et al. However the mean of total protein was 7.4 g/dL in OSMF and this was comparable to 7 gm/dL and 8.3 gm/dL as reported by AG Pathak et al. and Anuradha CD et al. respectively but in contrast to the findings of Patidar KA et al. in which the observed decrease in serum total proteins was 4.96 gm/dL [Table 3] and [Table 7].
|Table 7: Range and mean and standard deviation of total protein, albumin and globulin in group A and B|
Click here to view
The present study showed a marginal rise of albumin in OSMF group when compared with controls. This was in accordance with the study conducted by Anuradha CD et al. [Table 3] and [Table 7].
Similarly, there was a marginal decrease in globulin levels in patients with OSMF patients when compared with controls. [Table 3] and [Table 7] However, this difference was not statistically significant. This was in contrast to the studies done by AG Pathak et al. and Anuradha CD et al.
The reduced protein levels in OSMF patients could be either due to the reduced intake as a consequence of the disease process or the products of areca nut leading to atrophy of the gastrointestinal mucosa and impairing the absorption of the nutrients. However, none of the patients in the study had loss of weight.
The levels of protein, albumin, and globulin in the subjects of the study were as follows: OSMF group (Total Proteins)- 28 Subjects were in normal range, 2 patients showed increased levels; Control group (Total proteins)- 27 subjects were in normal range, and 3 showed an increase. All the subjects of both groups showed albumin in the normal range. OSMF group (Serum Globulin): 27 showed normal range, 3 showed an increase; Control group (serum globulin) 28 Subjects showed the normal range and 2 showed an increase. The ranges were according to the Seimens dade dimension. The analytical sensitivity of this method for total protein is ≤2.0 g/dL and for albumin is 0.6 g/dL [Table 3] and [Table 7].
The present study estimated the immunoglobulins using nephelometry method with Nephstar protein analysis system. Estimation of immunoglobulins in OSMF patients using RID technique was conducted by AG Pathak Rajendra et al., Dinesh Gupta et al., Remani et al., Naseema Shah et al., Pinakapani et al., Ketankuma et al. Our present study followed gm/l units as given by Nephstar analysis system. The IgG values in the present study were showing marginal rise in OSMF subjects when compared with controls (9.3-18.0 g/L and 9.7-16.9 g/L with mean and standard deviation of 14.578 ± 2.72 g/L and 14.053 ± 2.041 g/L). IgA values showed a decline in OSMF subjects on comparing with controls (1.0-6.2 g/l and 1.3-5.3 g/L with mean and standard deviation of 2.522 ± 1.15 g/l and 2.893 ± 1.05 g/L, respectively). These findings statistically significant. These observations were consistent with the study of Rajendran et al. which used RID and Divya et al. which used nephelometry [Table 4] and [Table 5].
The findings from our study along with that from the literature suggest that the there is immunological alterations observed in OSMF were almost similar to or nearer to those of oral cancer. However, in order to obtain more conclusive evidence, a larger study with evaluation of immunological parameters is necessary to evaluate if early analysis of immunological parameters will help in early detection of malignant transformation of OSMF.
| Conclusion|| |
The alteration in immunoglobulins observed in the OSMF group indicates the limited role of humoral immunity in OSMF. Further research with a larger group of patients is suggested so that we can obtain a clearer insight into the alterations of immunoglobulins in OSMF and role of humoral as well as cellular immunity in OSMF.
The clear association observed between stage of OSMF and duration of exposure to habits such as arecanut chewing provides with an opportunity for intervention by the primary dental care physicians. Intervention the form of counseling to give up harmful habits and awareness programs will bring down the incidence of malignant transformation of OSMF.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Wollina U, Verma SB, Ali FM, Patil K. Oral submucous fibrosis: An update. Clin Cosmet Investig Dermatol 2015;8:193-204.
Gupta SC, Yadav YC. “MISI” an etiologic factor in oral submucous fibrosis. Indian J Otolaryngol 1978;30:5-6.
Joshi SG. Fibrosis of the e palate and pillars. Ind J Otolaryngol 1953;4:1.
Pindborg J, Sirsat S. Oral submucous fibrosis. Oral Surg Oral Medi Oral Pathol 1966;22:764-79.
Kumar S, Singh R. Pterygium excision and conjunctival autograft: A comparative study of techniques. J Indian Acad Oral Med Radiol 2016;28:124-8. [Full text]
Chaturvedi V. Oral submucous fibrosis. Natl Med J India 1989;2:11-7.
Passi D, Bhanot P, Kacker D, Chahal D, Atri M, Panwar Y. Oral submucous fibrosis: Newer proposed classification with critical updates in pathogenesis and management strategies. Natl J Maxillofac Surg 2017;8:89-94.
] [Full text]
Phatak AG. Serum proteins and immunoglobulins in oral submucous fibrosis. Indian J Otolaryngol 1978;30:1.
Rajendran R. Oral submucous fibrosis: Etiology, pathogenesis, and future research. Bull World Health Organ 1994;72:985-96.
Remani P, Ankathil R, Vijayan KK, Haseena Beevi VM, Rajendran R, Vijayakumar T. Circulating immune complexes as an immunological marker in premalignant and malignant lesions of the oral cavity. Cancer Lett 1988;40:185-91.
Shah N, Kumar R, Shah MK. Immunological studies in oral submucous fibrosis. Indian J Dent Res 1994;5:81-7.
Anil S, Beena VT, Nair RG, Vijayakumar T. Evaluation of serum beta 2-microglobulin in premalignant and malignant lesions of the oral cavity. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1995;79:750-2.
Pinakapani R, Shambulingappa P, Shashikanth M. Salivary coagulopathy and immunoglobulins in oral submucous fibrosis. J Indian Acad Oral Med Radiol 2009;21:62-6. [Full text]
Marry NJ, Prashnath K, Jaysheel AS. Estimation of serum immunoglobulins [ IgG ] and [ IgA ] in patients with grade III and grade IV oral submucous fibrosis. J Cont Med A Dent 2016;4:66-9.
Prajapati KJ, Chawda JG. Estimation of major immunoglobulins in smokers and gutkha chewers. J Oral Maxillofac Pathol 2016;20:219-23.
] [Full text]
Kandasamy M, Jaisanghar N, Austin RD, Srivastava KC, Anusuya GS, Anisa N. Comparative evaluation of serum and salivary immunoglobulin G and A levels with total serum protein in oral submucous fibrosis patients: A case control study. J Pharm Bioallied Sci 2016;8(Suppl 1):S126-32.
Balakrishnan C, Aswath N. Estimation of serum, salivary immunoglobulin G, immunoglobulin A levels and total protein, hemoglobin in smokeless tobacco chewers and oral submucous fibrosis patients. Contemp Clin Dent 2015;6:157-62.
] [Full text]
Scully C. Serum IgG, IgA, IgM, IgD and IgE in lichen planus: No evidence for a humoral immunodeficiency. Clin Exp Dermatol 1982;7:163-70.
Divya V, Sathasivasubramanian S. Estimation of serum and salivary immunoglobulin G and immunoglobulin A in oral pre-cancer: A study in oral submucous fibrosis and oral lichen planus. J Nat Sci, Biol Med 2014;5:90-4.
Ganapathy KS, Gurudath S, Balikai B, Ballal S, Sujatha D. Role of iron deficiency in oral submucous fibrosis: An initiating or accelerating factor. J Indian Acad Oral Med Radiol 2011;23:25-8. [Full text]
Zameera A, Naik MG. Serum proteins, transaminases and blood urea in patients with oral submucous fibrosis- A Preliminary study. Int J Adv Res Oral Sci 2012;1:1-5.
Patidar KA, Parwani RN, Wanjari SP. Correlation of salivary and serum IgG, IgA levels with total protein in oral submucous fibrosis. J Oral Sci 2011;53:97-102.
Anuradha CD, Devi CS. Serum protein, ascorbic acid and iron and tissue collagen in oral submucous fibrosis-a preliminary study. Indian J Med Res 1993;98:147-51.
Gupta DS, Gupta M, Oswal RH. Estimation of major immunoglobulin profile in oral submucous fibrosis by radial immunodiffusion. Int J Oral Surg 1985;14:533-7.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]