Serologic Biomarkers in Pemphigus Monitoring: C-reactive Protein, Macrophage Migration Inhibitory Factor, and Prolactin Levels Versus Autoantibody Assays
-
Hossein Mortazavi
,
Vahide Saeidi
,
Kamran Balighi
,
Nafiseh Esmaeili
,
Amir Teimourpour
,
Maryam Daneshpazhooh
,
Shahin Hamzelou
,
Zahra Saffarian
,
Jafar Taghizadeh Fazli
Abstract
Evaluation and monitoring of pemphigus vulgaris (PV) typically involve autoantibody detection by enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence (IIF). We aimed to determine the levels of antipemphigus immunoglobulin (Ig) G autoantibodies using ELISA and IIF (as standard biomarkers), and compare it to prolactin, macrophage migration inhibitory factor (MIF), and C-reactive protein (CRP) (as nonstandard biomarkers) to determine which of these non-standard biomarkers is appropriate for PV monitoring. The experiment was performed before and during therapy.
Anti-Dsg immunoglobulin G autoantibodies were measured using ELISA and IIF (as standard biomarkers) versus prolactin, MIF, and CRP (nonstandard), before 1 and 3 months after the treatment. Before beginning the treatment, the severity of the disease was determined using the pemphigus disease area Index (PDAI). We enrolled 60 newly diagnosed patients with PV (32 men and 28 women; mean age=43.8±14.2 years).
Before treatment, the levels of anti-Dsg1, anti-Dsg3, and IIF were high and had a significant relationship with PDAI. PDAI also had a connection with the levels of CRP and prolactin. The anti-Dsg1, anti-Dsg3, IIF, and CRP titers decreased in patients treated with conventional (prednisolone plus azathioprine) and rituximab therapy during and after treatment.
In conclusion, anti-Dsg1, anti-Dsg3, and IIF autoantibody titers remain standard biomarkers for assessing disease activity, severity, and PV monitoring. The trend of CRP was similar to that of anti-Dsg1, anti-Dsg3, and IIF. Thus, CRP may be used for PV monitoring.
1. Daneshpazhooh M, Chams‐Davatchi C, Khamesipour A, Mansoori P, Taheri A, Firooz A, et al. Desmoglein 1 and 3 enzyme‐linked immunosorbent assay in Iranian patients with pemphigus vulgaris: correlation with phenotype, severity, and disease activity. J Eur Acad Dermatol Venereol. 2007;21(10):1319-24.
2. Mortazavi H, Shahdi M, Amirzargar AA, Naraghi ZS, Valikhani M, Daneshpazhooh M, et al. Desmoglein ELISA in the diagnosis of pemphigus and its correlation with the severity of pemphigus vulgaris. Iran J Allergy Asthma Immunol. 2009;8(1):53-6.
3. Saschenbrecker S, Karl I, Komorowski L, Probst C, Dähnrich C, Fechner K, et al. Serological Diagnosis of Autoimmune Bullous Skin Diseases. Front Immunol. 2019;10:1974.
4. Avgerinou G, Papafragkaki DK, Nasiopoulou A, Markantoni V, Arapaki A, Servitzoglou M, et al. Correlation of antibodies against desmogleins 1 and 3 with indirect immunofluorescence and disease status in a Greek population with pemphigus vulgaris. Correlation of antibodies against desmogleins 1 and 3 with indirect immunofluorescence and disease status in a Greek population with pemphigus vulgaris. 2013;27(4):430-5.
5. Mortazavi H, Kiavash K, Chams-Davatchi C, Esmaili N. Correlation of pemphigus vulgaris antibody titers by indirect immunofluorescence with activity of disease based on pemphigus area and activity score (PAAS). Acta Medica Iranica. 2008;46(3):239-44.
6. Chams-Davatchi C. Prevalence and treatment of pemphigus in Iran. Dermatol Clin. 2011;29(4):681-3.
7. Namazi MR, Fallahzadeh MK, Shaghelani H, Kamali‐Sarvestani E. Marked elevation of serum macrophage migration inhibitory factor levels in patients with pemphigus vulgaris. Int J Dermatol. 2010;49(2):146-8.
8. Yousefi M, Mozafari N, Hosseini MS, Gholamin S, Razavi SM, Namazi MR, et al. Evaluating serum prolactin and serum dehydroepiandrosterone sulfate levels in patients with pemphigus. Int J Dermatol. 2016
9. Farhad H, Nasrin S, Motahareh H, Taraneh T. Can we consider erythrocyte sedimentation rate and C-reactive protein as a severity index in pemphigus vulgaris? Int J Dermatol. 2017;20(3):84-8.
10. Severo JS, Santana AE, Aoki V, Michalany NS, Mantovani MM, Larsson CE, Jr., et al. Evaluation of C-reactive protein as an inflammatory marker of pemphigus foliaceus and superficial pyoderma in dogs. Vet Dermatol. 2018;29(2):128-e51.
11. Iraji F, Tajmirriahi N, Momeni I, Jamshidi K, Hashemzehi F, Siadat AH, et al. Do serum prolactin levels correlate with antibodies against desmoglein in pemphigus vulgaris? Adv Biomed Res. 2016;5:206.
12. Heckler I, Hong M, Amart Sinha A, Venkataraman I. Serological Biomarkers and Their Detection in Autoimmune Bullous Skin Diseases. Dermatol Pract Concept. 2022;12(2):e2022116.
13. Rosenbach M, Murrell DF, Bystryn JC, Dulay S, Dick S, Fakharzadeh S, et al. Reliability and convergent validity of two outcome instruments for pemphigus. J Invest Dermatol. 2009;129(10):2404-10.
14. Lajevardi V, Hallaji Z, Daneshpazhooh M, Ghandi N, Shekari P, Khani S. Evaluation of prolactin levels in patients with newly diagnosed pemphigus vulgaris and its correlation with pemphigus disease area index. Int J Womens Dermatol. 2016;2(2):53-5.
15. Kushner I, Antonelli MJ. What should we regard as an “elevated” C-reactive protein level? Annals Intern Med. 2015;163(4):326-.
16. Harman KE, Brown D, Exton LS, Groves RW, Hampton PJ, Mohd Mustapa MF, et al. British Association of Dermatologists' guidelines for the management of pemphigus vulgaris 2017. Br J Dermatol. 2017;177(5):1170-201.
17. Schmidt E, Dähnrich C, Rosemann A, Probst C, Komorowski L, Saschenbrecker S, et al. Novel ELISA systems for antibodies to desmoglein 1 and 3: correlation of disease activity with serum autoantibody levels in individual pemphigus patients. Exp Dermatol. 2010;19(5):458-63.
18. Mortazavi H, Khatami A, Seyedin Z, Vasheghani Farahani I, Daneshpazhooh M. Salivary desmoglein enzyme-linked immunosorbent assay for diagnosis of pemphigus vulgaris: a noninvasive alternative test to serum assessment. BioMed Res Int. 2015;2015.
19. Kanitakis J. Indirect immunofluorescence microscopy for the serological diagnosis of autoimmune blistering skin diseases. Clin Dermatol. 2001;19(5):614-21.
20. Barnadas MA, Rubiales M, Gich I, Gelpí C. Usefulness of specific anti‐desmoglein 1 and 3 enzyme‐linked immunoassay and indirect immunofluorescence in the evaluation of pemphigus activity. Int J Dermatol. 2015;54(11):1261-8.
21. Abasq C, Mouquet H, Gilbert D, Tron F, Grassi V, Musette P, et al. ELISA testing of anti–desmoglein 1 and 3 antibodies in the management of pemphigus. Arch Dermatol. 2009;145(5):529-35.
22. Alaeen H, Toosi R, Mahmoudi H, Balighi K, Tavakolpour S, Teimoupour A, et al. Short-term clinical and serological follow-up with conventional and conformational anti-desmoglein antibodies in treatment-naïve and previously treated patients with pemphigus vulgaris after receiving rituximab. Int J Womens Dermatol. 2019;5(5):372-7.
23. Genyk B. The Prognostic Value of the Change in the Concentration of C–Reactive Protein in the Oral Liquid of Patients with Acantholytic Pemphigus, in Varying Degrees of the Acantholytic Process Severity on the Mucous Membrane of the Oral Cavity. Arch Clin Med. 2018;24(2).
24. Mortazavi H, Esmaili N, Khezri S, Khamesipour A, Farahani IV, Daneshpazhooh M, et al. The effect of conventional immunosuppressive therapy on cytokine serum levels in pemphigus vulgaris patients. Iran J Allergy Asthma Immunol. 2014;13(3):174-83.
25. Rich RR. Clinical immunology: principles and practice. 5th ed: ELSEVIER; 2019.
26. Ghandi N, Tavassoli S, Ghiasi M, Lajevardi V, Abedini R, Tohidinik H-R, et al. Prolactin level changes in pemphigus vulgaris: A cohort study. Iran J Dermatol. 2016;19(2):35-9.
2. Mortazavi H, Shahdi M, Amirzargar AA, Naraghi ZS, Valikhani M, Daneshpazhooh M, et al. Desmoglein ELISA in the diagnosis of pemphigus and its correlation with the severity of pemphigus vulgaris. Iran J Allergy Asthma Immunol. 2009;8(1):53-6.
3. Saschenbrecker S, Karl I, Komorowski L, Probst C, Dähnrich C, Fechner K, et al. Serological Diagnosis of Autoimmune Bullous Skin Diseases. Front Immunol. 2019;10:1974.
4. Avgerinou G, Papafragkaki DK, Nasiopoulou A, Markantoni V, Arapaki A, Servitzoglou M, et al. Correlation of antibodies against desmogleins 1 and 3 with indirect immunofluorescence and disease status in a Greek population with pemphigus vulgaris. Correlation of antibodies against desmogleins 1 and 3 with indirect immunofluorescence and disease status in a Greek population with pemphigus vulgaris. 2013;27(4):430-5.
5. Mortazavi H, Kiavash K, Chams-Davatchi C, Esmaili N. Correlation of pemphigus vulgaris antibody titers by indirect immunofluorescence with activity of disease based on pemphigus area and activity score (PAAS). Acta Medica Iranica. 2008;46(3):239-44.
6. Chams-Davatchi C. Prevalence and treatment of pemphigus in Iran. Dermatol Clin. 2011;29(4):681-3.
7. Namazi MR, Fallahzadeh MK, Shaghelani H, Kamali‐Sarvestani E. Marked elevation of serum macrophage migration inhibitory factor levels in patients with pemphigus vulgaris. Int J Dermatol. 2010;49(2):146-8.
8. Yousefi M, Mozafari N, Hosseini MS, Gholamin S, Razavi SM, Namazi MR, et al. Evaluating serum prolactin and serum dehydroepiandrosterone sulfate levels in patients with pemphigus. Int J Dermatol. 2016
9. Farhad H, Nasrin S, Motahareh H, Taraneh T. Can we consider erythrocyte sedimentation rate and C-reactive protein as a severity index in pemphigus vulgaris? Int J Dermatol. 2017;20(3):84-8.
10. Severo JS, Santana AE, Aoki V, Michalany NS, Mantovani MM, Larsson CE, Jr., et al. Evaluation of C-reactive protein as an inflammatory marker of pemphigus foliaceus and superficial pyoderma in dogs. Vet Dermatol. 2018;29(2):128-e51.
11. Iraji F, Tajmirriahi N, Momeni I, Jamshidi K, Hashemzehi F, Siadat AH, et al. Do serum prolactin levels correlate with antibodies against desmoglein in pemphigus vulgaris? Adv Biomed Res. 2016;5:206.
12. Heckler I, Hong M, Amart Sinha A, Venkataraman I. Serological Biomarkers and Their Detection in Autoimmune Bullous Skin Diseases. Dermatol Pract Concept. 2022;12(2):e2022116.
13. Rosenbach M, Murrell DF, Bystryn JC, Dulay S, Dick S, Fakharzadeh S, et al. Reliability and convergent validity of two outcome instruments for pemphigus. J Invest Dermatol. 2009;129(10):2404-10.
14. Lajevardi V, Hallaji Z, Daneshpazhooh M, Ghandi N, Shekari P, Khani S. Evaluation of prolactin levels in patients with newly diagnosed pemphigus vulgaris and its correlation with pemphigus disease area index. Int J Womens Dermatol. 2016;2(2):53-5.
15. Kushner I, Antonelli MJ. What should we regard as an “elevated” C-reactive protein level? Annals Intern Med. 2015;163(4):326-.
16. Harman KE, Brown D, Exton LS, Groves RW, Hampton PJ, Mohd Mustapa MF, et al. British Association of Dermatologists' guidelines for the management of pemphigus vulgaris 2017. Br J Dermatol. 2017;177(5):1170-201.
17. Schmidt E, Dähnrich C, Rosemann A, Probst C, Komorowski L, Saschenbrecker S, et al. Novel ELISA systems for antibodies to desmoglein 1 and 3: correlation of disease activity with serum autoantibody levels in individual pemphigus patients. Exp Dermatol. 2010;19(5):458-63.
18. Mortazavi H, Khatami A, Seyedin Z, Vasheghani Farahani I, Daneshpazhooh M. Salivary desmoglein enzyme-linked immunosorbent assay for diagnosis of pemphigus vulgaris: a noninvasive alternative test to serum assessment. BioMed Res Int. 2015;2015.
19. Kanitakis J. Indirect immunofluorescence microscopy for the serological diagnosis of autoimmune blistering skin diseases. Clin Dermatol. 2001;19(5):614-21.
20. Barnadas MA, Rubiales M, Gich I, Gelpí C. Usefulness of specific anti‐desmoglein 1 and 3 enzyme‐linked immunoassay and indirect immunofluorescence in the evaluation of pemphigus activity. Int J Dermatol. 2015;54(11):1261-8.
21. Abasq C, Mouquet H, Gilbert D, Tron F, Grassi V, Musette P, et al. ELISA testing of anti–desmoglein 1 and 3 antibodies in the management of pemphigus. Arch Dermatol. 2009;145(5):529-35.
22. Alaeen H, Toosi R, Mahmoudi H, Balighi K, Tavakolpour S, Teimoupour A, et al. Short-term clinical and serological follow-up with conventional and conformational anti-desmoglein antibodies in treatment-naïve and previously treated patients with pemphigus vulgaris after receiving rituximab. Int J Womens Dermatol. 2019;5(5):372-7.
23. Genyk B. The Prognostic Value of the Change in the Concentration of C–Reactive Protein in the Oral Liquid of Patients with Acantholytic Pemphigus, in Varying Degrees of the Acantholytic Process Severity on the Mucous Membrane of the Oral Cavity. Arch Clin Med. 2018;24(2).
24. Mortazavi H, Esmaili N, Khezri S, Khamesipour A, Farahani IV, Daneshpazhooh M, et al. The effect of conventional immunosuppressive therapy on cytokine serum levels in pemphigus vulgaris patients. Iran J Allergy Asthma Immunol. 2014;13(3):174-83.
25. Rich RR. Clinical immunology: principles and practice. 5th ed: ELSEVIER; 2019.
26. Ghandi N, Tavassoli S, Ghiasi M, Lajevardi V, Abedini R, Tohidinik H-R, et al. Prolactin level changes in pemphigus vulgaris: A cohort study. Iran J Dermatol. 2016;19(2):35-9.
| Files | ||
| Issue | Vol 22 No 3 (2023) | |
| Section | Brief Communication | |
| DOI | https://doi.org/10.18502/ijaai.v22i3.13059 | |
| Keywords | ||
| Autoantibody C-reactive protein Desmogleins Macrophage migration inhibitory factor Pemphigus Prolactin | ||
| Rights and permissions | |
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Mortazavi H, Saeidi V, Balighi K, Esmaeili N, Teimourpour A, Daneshpazhooh M, Hamzelou S, Saffarian Z, Taghizadeh Fazli J. Serologic Biomarkers in Pemphigus Monitoring: C-reactive Protein, Macrophage Migration Inhibitory Factor, and Prolactin Levels Versus Autoantibody Assays. Iran J Allergy Asthma Immunol. 2023;22(3):312-318.
