Sinovitli osteoartrit hastalarında herpes virüsler ve parvovirüs B19’a karşı oluşan antikor yanıtının serum ve sinoviyal sıvıda araştırılması

Abstract

Amaç: Bu çalışmada diz ekleminde sinovit tanısı alan hastalarda, serum ve sinoviyal sıvıda sitomegalovirüs (CMV), Epstein-Barr virüsü (EBV), human herpes virüs-6 (HHV-6) ve parvovirüs B19’a karşı oluşan IgG yanıtlarının saptanması ve bu virüslere karşı oluşan spesifik lokal immun yanıtın, sinovit etiyolojisinin belirlenmesindeki rolünün araştırılması amaçlandı. Gereç ve Yöntem: Çalışmaya Bozok Üniversitesi Tıp Fakültesi Ortopedi ve Travmatoloji Polikliniği’ne müracaat eden Kellgren Lawrence sınıflamasına göre evre 3 ve 4  osteoartrit ve sinoviti mevcut olan yetişkinler, hasta grubu olarak alındı. Benzer yaş grubunda, diz ağrısı nedeniyle veya başka bir nedenle diz grafisi çekilen ancak Kellgren Lawrence sınıflamasına göre diz osteoartriti olmayan hastalar kontrol grubu olarak seçildi. Hasta grubuna 29 sinovitli olan hasta alındı ve kontrol grubu olarak da 31 hasta çalışmamıza dahil edildi. Sinovitli hastalardan sinoviyal sıvı ve serum örnekleri alınırken kontrol grubundan sadece serum örnekleri alındı. Tüm örneklerde anti-CMV, EBV, HHV-6 ve parvovirus B19 IgG antikorları mikro ELISA yöntemiyle araştırıldı. Sinoviyal ya da lokal antikor üretimini belirlemek için hasta grubuna ait tüm örneklerde albumin düzeyi spektrofotometrik yöntemle saptandı ve sinoviyal antikor indeksi (sABI) hesaplandı. Hasta ve kontrol grubuna ait tüm örneklerde anti- CMV, EBV, HHV-6 ve parvovirüs B19 IgG pozitiflik oranı araştırıldı. Hasta grubunda serum ve sinoviyadaki IgG düzeyi ve sinoviyal antikor indeksi (sABI) karşılaştırıldı. Bulgular: Tüm çalışma grubunda araştırılan virüsler için serumda IgG pozitifliği sırasıyla; CMV için %91, EBV için %85, parvovirus B19 için %36,6, HHV-6 içinse %43 olarak saptandı. Hasta serumlarında IgG poziflik oranı CMV ve EBV için en yüksekti ve sırasıyla; %100 ve 86 olarak saptandı. Kontrol grubunda EBV ve CMV IgG pozitiflik oranı %83 olarak saptandı. Hasta grubunda serumda parvovirus B19 ve HHV-6 IgG pozitiflik oranı ve absorbans değerleri kontrol grubuna göre daha yüksek saptandı. Hasta grubu serum ve sinoviyal antikor pozitifliği açısından karşılaştırıldığında; sinovitli olgularda lokal antikor üretiminin EBV IgG için %72,4 ile en fazla olduğu bunu %34,4 ile CMV IgG; % 27,5 ile parvovirus IgG ‘nin takip ettiği belirlendi. Sonuç: Sinovitli hastalarda serumda anti- EBV IgG, anti- CMV IgG ve anti-parvovirüs B19 IgG pozitiflik oranları kontrol grubuna göre daha yüksek idi. Sinovitli hastalarda sinoviyal kültür örneklerinde etkenin saptanmadığı durumlarda; CMV, EBV, HHV-6 ve parvovirüs-B19 gibi virüslerin etken olabileceğinin akılda tutulmasının ve hastalarda serum antikorlarına ilaveten sinoviyal sıvıda lokal antikor yanıtlarının araştırılması için antikor indeksinin belirlenmesinin de yararlı olacağı görüşündeyiz.

Keywords

• Sinovit
• CMV
• EBV
• HHV-6
• Parvovirüs B19

Investigation of antibody response against herpes viruses and parvovirus B19 in serum and synovial fluid in osteoarthritis patients with synovitis

Abstract

Aim: The aim of this study was to detect IgG responses against cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpes virus-6 (HHV-6) and parvovirus B19 in serum and synovial fluid in patients diagnosed with knee joint synovitis, and to investigate the role of specific local immune response against these viruses in detection of the etiology of synovitis. Material and Method: Adult patients with Grade 3 and 4 osteoarthritis and synovitis according to Kellgren-Lawrence classification who went into Bozok University Medical Faculty Hospital Orthopedics and Traumatology policlinic were included in the study as patient group. Patients in similar age group who had knee graphy because of knee pain or another reason but who didn’t have knee osteoarthritis according to Kellgren-Lawrence classification were chosen as control group. While 29 patients were included in patient group, 31 patients were included in control group. While synovial fluid and serum samples were taken from patients with synovitis, only serum samples were taken from control group. Anti-CMV,EBV, HHV-6 and parvovirus B19 IgG antibodies were analyzed with ELISA method in all serum samples. In order to determine synovial or local antibody production, albumin levels were detected in all samples belonging to patient group with spectrophotometric method as well as synovial antibody index (sABI) was calculated. Anti- CMV, EBV, HHV-6 and parvovirus B19 IgG positivity rate was investigated in samples of both patient and control groups. In patient group, IgG level in serum and synovial fluid and synovial antibody index (sABI) were compared. Results: For all viruses investigated in the study, IgG positivity rate in serum was detected as 91% for CMV, 85% for EBV, 36.6% for parvovirus B19 and 43% for HHV6. While the highest IgG positivity rates were found in CMV and EBV (100% and 86%, respectively) in patient group serums, IgG positivity rates for EBV and CMV were found 83% in control group serums. It was found that IgG positivity rates for parvovirus B19 and HHV-6 in serum and absorbance values were higher in patient group compared to control group. It was shown that in cases with synovitis, local antibody production was the highest for EBV IgG with 72.4%, and it was followed by CMV IgG (34.4%) and parvovirus IgG (27.5%). Conclusion: It was concluded that anti- EBV IgG, anti- CMV IgG, and anti-parvovirus B19 IgG positivity rates in serum were higher in patients with synovitis than control group. It should be kept in mind that viruses such as CMV, EBV, HHV-6 and parvovirüs-B19 can be considered as factors when the etiological agents cannot be detected in synovial culture samples in patients with synovitis, and it is believed that in addition to serum antibodies, determining the antibody index can be useful to investigate local antibody responses in synovial fluid in patients.

Keywords

• Synovitis
• CMV
• EBV
• HHV-6
• Parvovirus B19

References

1. Van de Sande MG, Baeten DL. Immunopathology of synovitis: from histology to molecular pathways. Rheumatology (Oxford) 2016; 55: 599-606.
2. Ene R, Sinescu RD, Ene P, Cirstoiu MM, Cirstoiu FC. Synovial inflammation in patients with different stages of knee osteoarthritis. Rom J Morphol Embryol 2015; 56: 169-73.
3. Orr C, Vieira-Sousa E, Boyle DL, et al. Synovial tissue research: a state-of-the-art review. Nat Rev Rheumatol 2017; 13: 463-75.
4. Sellam J, Berenbaum F. The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis. Nat Rev Rheumatol 2010; 6: 625-35.
5. de Lange-Brokaar BJ, Ioan-Facsinay A, Yusuf E, et al. Evolution of synovitis in osteoarthritic knees and its association with clinical features. Osteoarthritis Cartilage 2016; 24: 1867-74.
6. Swartz MN. Skin and soft tissue infections. In: Mandell GL, Bennett JE, Dolin R,eds. Mandell, Douglas and Bennett’s principles and practice of infectious diseases, 5th ed. Philadelphia: Churchill Livingstone, 2000.
7. Davignon JL, Combe B, Cantagrel A. Cytomegalovirus infection: friend or foe in rheumatoid arthritis? Arthritis Res Ther 2021; 23: 16.
8. Mathiessen A, Conaghan PG. Synovitis in osteoarthritis: current understanding with therapeutic implications. Arthritis Res Ther 2017; 19: 18.

9. Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis Cartilage 2013; 21: 16-21.
10. Hayashi D, Roemer FW, Katur A, et al. Imaging of synovitis in osteoarthritis: current status and outlook. Semin Arthritis Rheum 2011; 41: 116-30.
11. Scanzello CR, Goldring SR. The role of synovitis in osteoarthritis pathogenesis. Bone 2012; 51: 249-57.
12. Mehraein Y, Lennerz C, Ehlhardt S, Zang KD, Madry H. Replicative multivirus infection with cytomegalovirus, herpes simplex virus 1, and parvovirüs B19, and latent Epstein-Barr virus infection in the synovial tissue of a psoriatic arthritis patient. J Clin Virol 2004; 31: 25-31.
13. Takeda T, Mizugaki Y, Matsubara L, Imai S, Koike T, Takada K. Lytic Epstein-Barr virus infection in the synovial tissue of patients with rheumatoid arthritis. Arthritis Rheum 2000; 43: 1218-25.
14. Stahl HD, Hubner B, Seidl B, et al. Detection of multiple viral DNA species in synovial tissue and fluid of patients with early arthritis. Ann Rheum Dis 2000; 59: 342-6.
15. Alspaugh MA, Henle G, Lennette EL, Henle WJ. Elevated levels of antibodies to Epstein-Barr virus antigens in sera and synovial fluids of patients with rheumatoid arthritis. Clin Invest 1981; 67: 1134-40.
16. Mehraein Y, Lennerz C, Ehlhardt S, Remberger K, Ojak A, Zang KD. Latent Epstein-Barr virus (EBV) infection and cytomegalovirus (CMV) infection in synovial tissue of autoimmune chronic arthritis determined by RNA- and DNA-in situ hybridization. Mod Pathol 2004; 17: 781-9.
17. Aupiais C, Ilharreborde B, Doit C, et al. Aetiology of arthritis in hospitalised children: an observational study. Arch Dis Child 2015; 100: 742-7.
18. Miron D, Luder A, Horovitz Y, et al. Acute human parvovirüs B-19 infection in hospitalized children: A serologic and molecular survey. Pediatr Infect Dıs J 2006; 25: 898-901.
19. Moore TL. Parvovirüs-associated arthritis. Curr Opin Rheumatol 2000; 12: 289-94.
20. Perandones CE, Colmegna I, Arana RM. Parvovirüs B19: another agent associated with remitting seronegative symmetrical synovitis with pitting edema. J Rheumatol 2005; 32: 389-90.
21. Drago F, Ciccarese G, Agnoletti AF, et al. Remitting seronegative symmetrical synovitis with pitting edema associated with parvovirüs B19 infection: two new cases and review of the comorbidities. Int J Dermatol 2015; 54: e389-93.
22. Szumera M, Sikorska-Wisniewska G, Szweda P, Korzon M. Role of parvovirüs B19 as a causative agent for arthritis in children-- preliminary studies]. Med Wieku Rozwoj 2004; 8: 425-32.
23. Broccolo F, Drago F, Cassina G, et al. Selective reactivation of human herpesvirus 6 in patients with autoimmune connective tissue diseases. J Med Virol 2013; 85: 1925-34.
24. Alvarez-Lafuente R, Fernández-Gutiérrez B, de Miguel S, et al. Potential relationship between herpes viruses and rheumatoid arthritis: analysis with quantitative real time polymerase chain reaction. Ann Rheum Dis 2005; 64: 1357-9.