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Int. J. Life. Sci. Scienti. Res. eISSN: 2455-1716
Bisen, 2018
DOI:10.21276/ijlssr.2018.4.6.4
Copyright © 2015 - 2018| IJLSSR by Society for Scientific Research under a CC BY-NC 4.0 International License Volume 04 | Issue 06 | Page 2076
Seroprevalence of Rheumatoid Factor in Tertiary Care Hospital
Varad Vardhan Bisen
*
Assistant Professor, Department of Pathology, Government Medical College, Banda, India
*Address for Correspondence: Dr. Varad Vardhan Bisen, Assistant Professor, Department of Pathology, Government Medical
College Banda, Naraini Road, Uttar Pradesh-210001, India
Received: 02 Apr 2018/ Revised: 26 Jul 2018/ Accepted: 10 Oct 2018
ABSTRACT
Rheumatoid arthirits (RA) is a chronic inflammatory disorder that affects many tissues and organs but mainly affects the joints,
producing a proliferative and inflammatory disease that progresses to damage the joint cartilage and ankylosis of the joints. About
1% of the world’s population is affected by RA. Women three to five times more often than men, it is more common in age group
of 40 to 70 years of age. The useful serological markers for RA are Rheumatoid factor (RF) and antibodies to citrullinated peptides.
This present study was done to find out the prevalence of serological marker in suspected arthritis case in tertiary care hospital.
This prospective study was carried out in serology section in central pathology lab in Government Medical College, Banda from
April 2015 to August 2018. Total 776 blood samples were received for RA factor analysis. Out of 776 samples, 111 samples were
positive for RA factor 14.3% prevalence. Total 88 cases were females and 23 were males. Most common age group involved was
21 - 60 years in females and 40 - 70 years in males. For evaluation of patients with suspected RA, it is recommended to perform
anti-cyclic citrullinated peptide antibody and RF analysis to increase specificity of the results.
Key-words: Rheumatoid Arthiritis, RA Factor, Citrullinated, Anti-CCP, Serological marker
INTRODUCTION
Rheumatoid Arthritis is a chronic s inflammatory disorder
that may affect many tissues and organs but mainly
attacks the joints, producing a proliferative and
inflammatory synovitis that often progresses to involve
the articular cartilage and ankylosis of the joints.
About 1% of the world’s population is affected by RA [1,2]
women three to five times more common than men. It is
most common in those 40 to 70 years of age. The clinical
course is not consistent. The disease begins slowly in
more than half of the affected individuals. Initially there
is weakness, fatigue and generalized musculoskeletal
pain and after many weeks to months joints become
involved. Symmetrically small joints are involved before
the larger joints. Symptoms usually develop in wrist and
feet with ankles, elbows and knees. RA is diagnosed
according to clinical findings and serological testing.
How to cite this article
Bisen VV. Seroprevalence of Rheumatoid Factor in Tertiary Care
Hospital. Int. J. Life. Sci. Scienti. Res., 2018; 4(6): 2076-2079.
Access this article online
www.ijlssr.com
The main serological markers are RA factor and Anti-CCP.
Rheumatoid factor is mainly IgM antibody, but it can also
be IgA, IgG or IgE isotype directed against Fc portion of
IgG of human or animal. It is found in 60% to 90% of
rheumatoid arthritis patients [3,4]
. Three RF isotypes (IgM,
IgA, and IgG) are detected in up to 52% of RA patients
but in fewer than 5% of patients with other connective
tissue diseases. Increase in Both IgM and IgA RF factor is
almost exclusively seen in RA patients [5,6]
. The present
study was done to know the sero-prevalence of
serological marker in clinically suspected arthritis case in
tertiary care hospital.
MATERIALS AND METHODS
This original preliminary prevalence study was carried
out in serology section in Central pathology lab in
Government Medical College, Banda from April 2015 to
August, 2018. Total 776 blood samples were received for
RA factor Analysis. Blood samples were centrifuged in
3000 rpm and Sera Separated.
RA factor was determined quantitatively by
Immunoturbidimetric analysis, using turbilatex RF
(Accurex Biomedical Kit). RF kit contains latex particles
coated with human gamma globulin which reacts with RF
in the sample resulting in the Agglutination. This
Research Article
Int. J. Life. Sci. Scienti. Res. eISSN: 2455-1716
Bisen, 2018
DOI:10.21276/ijlssr.2018.4.6.4
Copyright © 2015 - 2018| IJLSSR by Society for Scientific Research under a CC BY-NC 4.0 International License Volume 04 | Issue 06 | Page 2077
agglutination causes change in absorbance, which is
measured at 650 nm and it is proportional to the
concentration of RF. RF factor is measured by the fully
automated Spectrophotometric analyzer. RF factor value
above 20 IU/L is considered significant.
RESULTS
Out of the 776 samples, 111 samples were positive for
RA Factor 14.3% prevalence (Table 1). This study was
done in Cameroon and showed the prevalence of 5.4%
[7]
, where as a similar study in Cote d Ivoire showed
prevalence of 7% among people aged between 3 - 70
years [8]
. Study done by Chandrashekhar et al. [9]
showed
a prevalence of 7% in the age group of 21 - 60 years
whereas study done by Sucilathangam et al. [10]
reported
a 10.6 % prevalence of RA factor. Study by Alghuweri et
al. [11]
has high prevalence of Rheumatoid factor, which
was 81.7 % in their study. Out of 111 samples, which
were positive for RA factor, 88 were females (79.28%)
and 23 were males (20.72%). Most positive cases in
females were in the age group of 21 - 60 years, and in
males in the age group of 40 - 70 years (Table 2). Female
to male ratio of positivity was of around 4:1. Youngest
female patient was 16 yrs of age and youngest male was
18 years of age. Out of total 776 samples, 512 samples
were of females and 264 samples were of males. Total
17.1% positivity prevalence was seen female patient age
group. Total 88 cases were positive out of 512, where as
in males it was around 8.7%, 23 cases positive out of 264
samples tested (Table 3). All positive samples showed
results above 20 IU/L (Highest being of value >900 IU/L
of 38 year old female patient), which considered
significant in RF analysis by immunoturbidimetric
method.
Table 1: Total number of positive cases with percentage
prevalence
Total Number
Total positive cases 111
Total sample tested 776
Percentage prevalence 14.3%
Table 2: Age and sex wise distribution of positive cases
Age group
Number of
Females
Number of
Males
10-20 3 2
21-30 24 -
31-40 19 3
41-50 20 8
51-60 17 -
61-70 5 8
>70 - 2
Total 88 23
Table 3: Sex wise distribution of positive cases
Sex Total sample
tested
Total positive
cases
Males 264 23
Females 512 88
Total 776 111
DISCUSSION
Our study has showed more females produced RA factor
than males. This can be explained by the involvement
and influence of female sex hormones on autoimmunity.
Female hormones play a role in the initiation and/or
worsening of the disease as seen by the risk induced by
estrogen-progestin pills, pregnancy, and the postpartum
period [12]
. Rheumatoid factor was present in people
aged 16 - 70 years and absent beyond 70 years. Some
studies have shown that several autoimmune diseases,
including RA can occur at any age but mostly between 30
and 60 years. Beyond this age, the rate decreases
gradually [13]
. The aging is also accompanied by
decreased immunity, alteration of T lymphocyte
cooperation with B Lymphocytes, decreased B cell
survival and dysfunction of co-stimulatory pathways [24]
.
Int. J. Life. Sci. Scienti. Res. eISSN: 2455-1716
Bisen, 2018
DOI:10.21276/ijlssr.2018.4.6.4
Copyright © 2015 - 2018| IJLSSR by Society for Scientific Research under a CC BY-NC 4.0 International License Volume 04 | Issue 06 | Page 2078
In Finland the prevalence of RF positive RA adults were
reported to be 0.7%. The annual adults were reported to
be 0.7%. The annual incidence has varied from 32 to 42
per 100000 in different studies during the past two
decades [14]
. In England the Prevalence of a false positive
RF reaction was seen much higher in polluted areas than
in less polluted areas [15]
. The prevalence of RA is 0.5-1%
among adults in Europe but it seems to be much lower in
some Asian and African Populations [16]
.
RF positive patients with R.A. may experience more
serious and erosive joint disease and extra articular
manifestations than those who are R.F. negative.
Rheumatoid factor is also found in many other diseases
including other connective tissue disease like Sjogren
syndrome, systemic lupus erythematosus, mixed
connective tissue diseases, chronic infection and in
healthy elderly population. Patients with Sjogrens
syndrome and Type II and Type III mixed
cryoglobulinemia have the maximum titre [17,18]
.
Presently the main clinically useful markers in patients
with RA are Rheumatoid factors and antibodies to
citrullinated peptides for both diagnosis and Radiological
changes. R.F. Testing in RA patients has a sensitivity of
60% to 90% and a specificity of 85% [3,4]
. ESR and CRP for
aiding in assessment of disease activity, predicting
functional, and Radiographic Outcomes.
It has been recognized that RFs have an important role in
the differential diagnosis of Multi-arthiritis because they
make it possible to identify RA patients [19]
. RF testing has
been one of the classification criteria for RA since 1987
and their role in Classification of RA has been confirmed
by the updated criteria [20,21]
. To assess the patients with
suspected RA, It is recommended to perform anti-cyclic
citrullinated peptide antibody and IgM RF to increase the
specificity of the results.
A metanalysis has shown that the pooled sensitivities of
ACPA and RF are similar, but ACPA positivity is more
specific for RA than IgM RF and more specific for early
RA.[22,23]
CONCLUSIONS
Prevalence of RA factor was 14.3%, females almost 4
times more positive than males. Positivity of RA factor
was not seen above 70 years of age which may be due to
decreased immunity and decreased alteration of
co-stimulatory pathways. RA factor alone is less specific
as a marker for diagnosis of RA; hence Anti-CCP needs to
be added in testing in order to increase the specificity of
the test, especially for early suspected RA patients. This
preliminary study provides insight of prevalence of RA
factor in rural population of Banda district in Uttar
Pradesh, in reference of their Age and Sex. Detailed
study is required to correlate the prevalence of RA factor
with other non-rheumatic diseases. Further studies are
required to study the impact of geographic,
epidemiologic pattern and to draw conclusions
specifically treatment patterns for RA.
ACKNOWLEDGMENTS
Author Acknowledge all the technical staff of the
serology section of the Government Medical College for
the help, support and for collection of data in writing of
this article.
CONTRIBUTION OF AUTHORS
No contribution other than that from the corresponding
author was given in writing this Research Paper.
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Int. J. Life. Sci. Scienti. Res. eISSN: 2455-1716
Bisen, 2018
DOI:10.21276/ijlssr.2018.4.6.4
Copyright © 2015 - 2018| IJLSSR by Society for Scientific Research under a CC BY-NC 4.0 International License Volume 04 | Issue 06 | Page 2079
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[22]Bas S, Genevay S, Meyer O, Gabay C. Anti-cyclic
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rheumatoid arthritis. Rheumatology, 2003; 42(5):
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[24] Menzel EJ, Zlabinger GJ, Dunky A, Steffen C.
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Open Access Policy:
Authors/Contributors are responsible for originality, contents, correct references, and ethical issues. IJLSSR publishes all articles under Creative
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Seroprevalence of Rheumatoid Factor in Tertiary Care Hospital

  • 1. Int. J. Life. Sci. Scienti. Res. eISSN: 2455-1716 Bisen, 2018 DOI:10.21276/ijlssr.2018.4.6.4 Copyright © 2015 - 2018| IJLSSR by Society for Scientific Research under a CC BY-NC 4.0 International License Volume 04 | Issue 06 | Page 2076 Seroprevalence of Rheumatoid Factor in Tertiary Care Hospital Varad Vardhan Bisen * Assistant Professor, Department of Pathology, Government Medical College, Banda, India *Address for Correspondence: Dr. Varad Vardhan Bisen, Assistant Professor, Department of Pathology, Government Medical College Banda, Naraini Road, Uttar Pradesh-210001, India Received: 02 Apr 2018/ Revised: 26 Jul 2018/ Accepted: 10 Oct 2018 ABSTRACT Rheumatoid arthirits (RA) is a chronic inflammatory disorder that affects many tissues and organs but mainly affects the joints, producing a proliferative and inflammatory disease that progresses to damage the joint cartilage and ankylosis of the joints. About 1% of the world’s population is affected by RA. Women three to five times more often than men, it is more common in age group of 40 to 70 years of age. The useful serological markers for RA are Rheumatoid factor (RF) and antibodies to citrullinated peptides. This present study was done to find out the prevalence of serological marker in suspected arthritis case in tertiary care hospital. This prospective study was carried out in serology section in central pathology lab in Government Medical College, Banda from April 2015 to August 2018. Total 776 blood samples were received for RA factor analysis. Out of 776 samples, 111 samples were positive for RA factor 14.3% prevalence. Total 88 cases were females and 23 were males. Most common age group involved was 21 - 60 years in females and 40 - 70 years in males. For evaluation of patients with suspected RA, it is recommended to perform anti-cyclic citrullinated peptide antibody and RF analysis to increase specificity of the results. Key-words: Rheumatoid Arthiritis, RA Factor, Citrullinated, Anti-CCP, Serological marker INTRODUCTION Rheumatoid Arthritis is a chronic s inflammatory disorder that may affect many tissues and organs but mainly attacks the joints, producing a proliferative and inflammatory synovitis that often progresses to involve the articular cartilage and ankylosis of the joints. About 1% of the world’s population is affected by RA [1,2] women three to five times more common than men. It is most common in those 40 to 70 years of age. The clinical course is not consistent. The disease begins slowly in more than half of the affected individuals. Initially there is weakness, fatigue and generalized musculoskeletal pain and after many weeks to months joints become involved. Symmetrically small joints are involved before the larger joints. Symptoms usually develop in wrist and feet with ankles, elbows and knees. RA is diagnosed according to clinical findings and serological testing. How to cite this article Bisen VV. Seroprevalence of Rheumatoid Factor in Tertiary Care Hospital. Int. J. Life. Sci. Scienti. Res., 2018; 4(6): 2076-2079. Access this article online www.ijlssr.com The main serological markers are RA factor and Anti-CCP. Rheumatoid factor is mainly IgM antibody, but it can also be IgA, IgG or IgE isotype directed against Fc portion of IgG of human or animal. It is found in 60% to 90% of rheumatoid arthritis patients [3,4] . Three RF isotypes (IgM, IgA, and IgG) are detected in up to 52% of RA patients but in fewer than 5% of patients with other connective tissue diseases. Increase in Both IgM and IgA RF factor is almost exclusively seen in RA patients [5,6] . The present study was done to know the sero-prevalence of serological marker in clinically suspected arthritis case in tertiary care hospital. MATERIALS AND METHODS This original preliminary prevalence study was carried out in serology section in Central pathology lab in Government Medical College, Banda from April 2015 to August, 2018. Total 776 blood samples were received for RA factor Analysis. Blood samples were centrifuged in 3000 rpm and Sera Separated. RA factor was determined quantitatively by Immunoturbidimetric analysis, using turbilatex RF (Accurex Biomedical Kit). RF kit contains latex particles coated with human gamma globulin which reacts with RF in the sample resulting in the Agglutination. This Research Article
  • 2. Int. J. Life. Sci. Scienti. Res. eISSN: 2455-1716 Bisen, 2018 DOI:10.21276/ijlssr.2018.4.6.4 Copyright © 2015 - 2018| IJLSSR by Society for Scientific Research under a CC BY-NC 4.0 International License Volume 04 | Issue 06 | Page 2077 agglutination causes change in absorbance, which is measured at 650 nm and it is proportional to the concentration of RF. RF factor is measured by the fully automated Spectrophotometric analyzer. RF factor value above 20 IU/L is considered significant. RESULTS Out of the 776 samples, 111 samples were positive for RA Factor 14.3% prevalence (Table 1). This study was done in Cameroon and showed the prevalence of 5.4% [7] , where as a similar study in Cote d Ivoire showed prevalence of 7% among people aged between 3 - 70 years [8] . Study done by Chandrashekhar et al. [9] showed a prevalence of 7% in the age group of 21 - 60 years whereas study done by Sucilathangam et al. [10] reported a 10.6 % prevalence of RA factor. Study by Alghuweri et al. [11] has high prevalence of Rheumatoid factor, which was 81.7 % in their study. Out of 111 samples, which were positive for RA factor, 88 were females (79.28%) and 23 were males (20.72%). Most positive cases in females were in the age group of 21 - 60 years, and in males in the age group of 40 - 70 years (Table 2). Female to male ratio of positivity was of around 4:1. Youngest female patient was 16 yrs of age and youngest male was 18 years of age. Out of total 776 samples, 512 samples were of females and 264 samples were of males. Total 17.1% positivity prevalence was seen female patient age group. Total 88 cases were positive out of 512, where as in males it was around 8.7%, 23 cases positive out of 264 samples tested (Table 3). All positive samples showed results above 20 IU/L (Highest being of value >900 IU/L of 38 year old female patient), which considered significant in RF analysis by immunoturbidimetric method. Table 1: Total number of positive cases with percentage prevalence Total Number Total positive cases 111 Total sample tested 776 Percentage prevalence 14.3% Table 2: Age and sex wise distribution of positive cases Age group Number of Females Number of Males 10-20 3 2 21-30 24 - 31-40 19 3 41-50 20 8 51-60 17 - 61-70 5 8 >70 - 2 Total 88 23 Table 3: Sex wise distribution of positive cases Sex Total sample tested Total positive cases Males 264 23 Females 512 88 Total 776 111 DISCUSSION Our study has showed more females produced RA factor than males. This can be explained by the involvement and influence of female sex hormones on autoimmunity. Female hormones play a role in the initiation and/or worsening of the disease as seen by the risk induced by estrogen-progestin pills, pregnancy, and the postpartum period [12] . Rheumatoid factor was present in people aged 16 - 70 years and absent beyond 70 years. Some studies have shown that several autoimmune diseases, including RA can occur at any age but mostly between 30 and 60 years. Beyond this age, the rate decreases gradually [13] . The aging is also accompanied by decreased immunity, alteration of T lymphocyte cooperation with B Lymphocytes, decreased B cell survival and dysfunction of co-stimulatory pathways [24] .
  • 3. Int. J. Life. Sci. Scienti. Res. eISSN: 2455-1716 Bisen, 2018 DOI:10.21276/ijlssr.2018.4.6.4 Copyright © 2015 - 2018| IJLSSR by Society for Scientific Research under a CC BY-NC 4.0 International License Volume 04 | Issue 06 | Page 2078 In Finland the prevalence of RF positive RA adults were reported to be 0.7%. The annual adults were reported to be 0.7%. The annual incidence has varied from 32 to 42 per 100000 in different studies during the past two decades [14] . In England the Prevalence of a false positive RF reaction was seen much higher in polluted areas than in less polluted areas [15] . The prevalence of RA is 0.5-1% among adults in Europe but it seems to be much lower in some Asian and African Populations [16] . RF positive patients with R.A. may experience more serious and erosive joint disease and extra articular manifestations than those who are R.F. negative. Rheumatoid factor is also found in many other diseases including other connective tissue disease like Sjogren syndrome, systemic lupus erythematosus, mixed connective tissue diseases, chronic infection and in healthy elderly population. Patients with Sjogrens syndrome and Type II and Type III mixed cryoglobulinemia have the maximum titre [17,18] . Presently the main clinically useful markers in patients with RA are Rheumatoid factors and antibodies to citrullinated peptides for both diagnosis and Radiological changes. R.F. Testing in RA patients has a sensitivity of 60% to 90% and a specificity of 85% [3,4] . ESR and CRP for aiding in assessment of disease activity, predicting functional, and Radiographic Outcomes. It has been recognized that RFs have an important role in the differential diagnosis of Multi-arthiritis because they make it possible to identify RA patients [19] . RF testing has been one of the classification criteria for RA since 1987 and their role in Classification of RA has been confirmed by the updated criteria [20,21] . To assess the patients with suspected RA, It is recommended to perform anti-cyclic citrullinated peptide antibody and IgM RF to increase the specificity of the results. A metanalysis has shown that the pooled sensitivities of ACPA and RF are similar, but ACPA positivity is more specific for RA than IgM RF and more specific for early RA.[22,23] CONCLUSIONS Prevalence of RA factor was 14.3%, females almost 4 times more positive than males. Positivity of RA factor was not seen above 70 years of age which may be due to decreased immunity and decreased alteration of co-stimulatory pathways. RA factor alone is less specific as a marker for diagnosis of RA; hence Anti-CCP needs to be added in testing in order to increase the specificity of the test, especially for early suspected RA patients. This preliminary study provides insight of prevalence of RA factor in rural population of Banda district in Uttar Pradesh, in reference of their Age and Sex. Detailed study is required to correlate the prevalence of RA factor with other non-rheumatic diseases. Further studies are required to study the impact of geographic, epidemiologic pattern and to draw conclusions specifically treatment patterns for RA. ACKNOWLEDGMENTS Author Acknowledge all the technical staff of the serology section of the Government Medical College for the help, support and for collection of data in writing of this article. CONTRIBUTION OF AUTHORS No contribution other than that from the corresponding author was given in writing this Research Paper. REFERENCES [1] Scott DL, Wolfe F, Huizinga TW, Rheumatoid arthritis. Lancet, 2010; 376(9746): 1094-108. [2] Carmona L, Cross M, Williams B, Lassere M, March L, Rheumatoid arthritis. Best Pract Res Clin Rheumato, 2010; 24: 733–45. [3] Nishimura K, Sugiyama D, Kogata Y, et al. Meta analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis. Annals of Internal Medicine, 2007; 146(11): 797–808. [4] Nell VPK, Machold KP, Stamm TA, et al. Autoantibody profiling as early diagnostic and prognostic tool for rheumatoid arthritis. Annals of the Rheumatic Diseases, 2005; 64(12): 1731–1736. [5] Jonsson T, Steinsson K, Jónsson H, Geirsson AJ, Thorsteinsson J, Valdimarsson H. Combined elevation of IgM and IgA rheumatoid factor has high diagnostic specificity for rheumatoid arthritis. Rheumatology International, 1998; 18(3): 119–122. [6] Jonsson T, Valdimarsson H. What about IgA rheumatoid factor in rheumatoid arthritis? Annals of the Rheumatic Diseases, 1998; 57(1): 63–64.
  • 4. Int. J. Life. Sci. Scienti. Res. eISSN: 2455-1716 Bisen, 2018 DOI:10.21276/ijlssr.2018.4.6.4 Copyright © 2015 - 2018| IJLSSR by Society for Scientific Research under a CC BY-NC 4.0 International License Volume 04 | Issue 06 | Page 2079 [7] Etienne Philemon Atabonkeng, DieudonnE Adiogo et al. Evaluation of the Prevalence of Rheumatoid Factor in Five Regions of Cameroon. Arch Rheumatology, 2015: 30(5): 226-230. [8] Viatte S, Flynn E, Lunt M, Barnes J, Singwe-Ngandeu M, Bas S, et al. Investigation of Caucasian rheumatoid arthritis susceptibility loci in African patients with the same disease. Arthritis Res Ther., 2012; 14: 239. [9] Chandrasekhar S, Koripella R. Seroprevalence of Rheumatoid Factor in Arthritis Cases in a Tertiary Care Hospital. Int. J. Curr. Microbiol. App. Sci., 2017; 6(12): 1925-1928. [10]Sucilathangam G, Smiline G, Velvizhi G, Revathy C. Int. J. Curr. Microbiol. App. Sci., 2015; 4(9): 61-66. [11]Alghuweri A, Marafi A, Alhiary M. Use of serological markers for evaluation patients with rheumatoid arthritis, Int J Biol Med Res., 2012; 3(1): 1397-1398. [12]Klemmer N, Vittecoq O. Rheumatoid arthritis and environmental factors. The Rheumatologist's Newsletter, 2004; 307 (4): 21-25 [13]Morel J, Combe B. How to predict prognosis in early rheumatoid arthritis. Best Pract Res Clin Rheumatol., 2005; 19(1): 137-46. [14]Aho K, Heliovaara M, Sievers K, Maatela J, Isomaki H. Clinical arthritis associated with positive radiological and serological findings in Finnish adults. Rheumatol Int., 1989; 9 (1): 7–11 [15]Heliovaara M, Aho K, Knekt P, Impivaara O, Reunanen A, Aromaa A. Coffee consumption, rheumatoid factor, and the risk of rheumatoid arthritis. Ann Rheum Dis., 2000; 59: 631–635. [16]Silman AJ. Rheumatoid arthritis. In: Silman AJ, Hochberg MC, eds. Epidemiology of the rheumatic diseases. 2nd ed. Oxford: Oxford University Press, 2001: 31–71. [17] Diaz-Lopez C, Geli C, Corominas H, et al. Are there clinical or serological differences between male and female patients with primary Sjogren’s syndrome? Journal of Rheumatology, 2004; 31[7]:1352–1355. [18]Sansonno D, Lauletta G, Nisi L, et al. Non-enveloped HCV core protein as constitutive antigen of cold-precipitable immune complexes in type II mixed cryoglobulinaemia. Clinical and Experimental Immunology, 2003; 133(2): 275–282. [19]Miller A, Mahtani KR, Waterfield MA, Timms A, Misbah SA, Luqmani RA. Is rheumatoid factor useful in primary care? A retrospective cross-sectional study. Clinical Rheumatology, 2013; 32(7): 1089- 1093. [20] Arnett FC, Edworthy SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis and Rheumatism, 1988; 31(3): 315–324. [21] Aletaha D, Neogi T, Silman AJ, et al. Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis and Rheumatism, 2010; 62(9): 2569–2581. [22]Bas S, Genevay S, Meyer O, Gabay C. Anti-cyclic citrullinated peptide antibodies, IgM and IgA rheumatoid factors in the diagnosis and prognosis of rheumatoid arthritis. Rheumatology, 2003; 42(5): 677–680. [23] Rantapaa- Dahlqvist S, De Jong BAW, Berglin E, et al. Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis and Rheumatism, 2003; 48(10): 2741–2749. [24] Menzel EJ, Zlabinger GJ, Dunky A, Steffen C. Autoimmunity and T-cell subpopulations in old age. Arch Gerontol Geriatr., 1988; 7(4): 249-260. Open Access Policy: Authors/Contributors are responsible for originality, contents, correct references, and ethical issues. IJLSSR publishes all articles under Creative Commons Attribution- Non-Commercial 4.0 International License (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/legalcode