Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 35  |  Issue : 3  |  Page : 1038-1042

Protein 70 in alopecia areata


1 Department of Dermatology, Andrology & S.T.Ds, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Medical Biochemistry & Molecular Biology, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Date of Submission01-Jan-2022
Date of Decision26-Feb-2022
Date of Acceptance27-Feb-2022
Date of Web Publication29-Oct-2022

Correspondence Address:
Aya H M. Elgendy
Shebin Elkom, Menoufia
Egypt
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_2_22

Rights and Permissions
  Abstract 


Background
Heat shock proteins (HSPs) are proteins that are expressed under a variety of stresses. How stresses and HSPs affect alopecia areata (AA) is not fully understood.
Objectives
To evaluate the possible role of serum level of HSP70 in the pathogenesis of AA.
Patients and methods
The current work examined 43 individuals with AA and 40 analogous age-matched and sex-matched healthy controls. Patients underwent full history taking, clinical examination, and investigations (HSP70 serum levels using the enzyme-linked immunosorbent assay). The data were analyzed using the SPSS software.
Results
In the current study, among patients, serum HSP70 ranged between 3 and 135 ng/ml with a mean of 22.45 ± 25.916, while in controls, it ranged between 4 and 106 ng/ml with a mean of 21.47 ± 24.315, with no significant difference between AA patients and controls regarding their serum HSP70 level (P = 0.616).
Conclusion
There was no significant difference between AA patients and controls regarding their serum HSP70 level. So future research and large-scale studies on different population and ethnicities are needed for a firmer conclusion.

Keywords: alopecia areata, Biomarker, enzyme-linked immunosorbent assay, heat shock protein 70, immune response, nitric oxide compounds, ophiasis, serum level, severity, stress


How to cite this article:
Soliman MM, Elgendy AH, Arafat ES. Protein 70 in alopecia areata. Menoufia Med J 2022;35:1038-42

How to cite this URL:
Soliman MM, Elgendy AH, Arafat ES. Protein 70 in alopecia areata. Menoufia Med J [serial online] 2022 [cited 2024 Mar 28];35:1038-42. Available from: http://www.mmj.eg.net/text.asp?2022/35/3/1038/359471




  Introduction Top


Alopecia areata (AA) is a common inflammatory nonscarring type of hair loss. Significant variations in the clinical presentation of AA have been observed ranging from small, well-circumscribed patches of hair loss to complete absence of body and scalp hair[1].

The cause of AA is not completely clear and its incidence may be related to genetic, autoimmune, and environmental factors[2],[3].

Heat shock proteins (HSPs) are certain proteins that are expressed under a variety of stresses including heat, heavy metals, toxins, oxidants, and infections and play a major role in protecting cells against damage under stressful conditions[4]. They are mainly involved in the proper folding of other proteins and, hence, referred to as molecular chaperons. The accumulation of HSPs is seen in pathologic conditions and tumors[5]. Depending on its intracellular or extracellular location, HSP70 fulfils different functions. Intracellular HSP70 protects cells against lethal damage induced by stress, supports the synthesis and transport of other proteins, and prevents misfolding and aggregation. Extracellular and cell surface-bound HSP70 plays an essential role in eliciting immune responses[6].

The aim of the current study was to evaluate the possible role of serum level of HSP70 in the pathogenesis of AA.


  Patients and methods Top


This case–control study was carried out on 83 participants; 43 AA patients and 40 apparently age-matched and sex-matched healthy controls. They were recruited from the Dermatology Outpatient Clinic of Menoufia University Hospital, after exclusion of obese patients, those with dermatological diseases other than AA, patients suffering from any systemic or autoimmune disorder, smokers, present or past history of cardiovascular or brain ischemic heart disease, use of antibiotics, hormonal therapy, nitric oxide compounds and heavy metals since one month, existence of nonepithelial ovarian cancer, breast, lung, pancreas cancer, and presence of occupational chronic psychological stress.

A written consent form approved by the Local Ethics Research Committee in Menoufia Faculty of Medicine was obtained from every participant before study initiation after explanation of the study nature and procedure.

The diagnosis of AA was made based on the patient's history and the typical clinical feature which ranged from small, well-circumscribed patches of hair loss to complete absence of body and scalp hair.

All patients included in the study were subjected to full history taking including onset, course, and duration of alopecia, family history, occupational history, previous treatment methods used, history of other diseases, general, dermatological examination including scalp examination for clinical types of AA, its site, severity assessment according to alopecia areata progression index (AAPI) and severity of alopecia tool (SALT) score and dermoscopic evaluation.

Collection and preparation of samples: 5 ml of venous blood was collected from all participants using disposable sterilized plastic syringes under complete aseptic conditions and thrown into a plain test tube at room temperature for 10–20 min and were centrifuged for 20 min at a speed of 2000–3000 rpm and the serum of patients and the control group were separated and stored at −20°C. After collecting all the control samples, in one day all the samples were extracted from the freezer, defreezed, homogenized, and prepared for the measurement of HSP70 by the commercially available enzyme-linked immunosorbent assay kits. The human HSP70 enzyme-linked immunosorbent assay kits were supplied by Sunred Company, Shanghai, China.

Statistical analysis

All the data were to undergo collection, tabulation, and statistical analysis by an IBM personal computer with the Statistical Package for the Social Sciences (SPSS) version 22 (SPSS Inc., Chicago, Illinois, USA), where the following statistics were used: Descriptive statistics in the form of range, mean, and SD; presented the quantitative and qualitative data in the form of percentages and numbers. Analytical statistics were used to detect the possible correlation between the targeted disease and studied factors. The used test of significance included: χ2 test was used to study the correlation between two qualitative variables; Mann–Whitney test (U) was used in comparison between two groups not normally distributed having quantitative variables; and Kruskal–Wallis test was used in comparison between three or more groups not normally distributed having quantitative variables. Spearman's correlation coefficient (rs) was used to study the correlation between nonparametric quantitative variables. P value less than 0.05 was considered significant. P value more than 0.05 was considered nonsignificant. P value less than 0.001 was considered highly significant statistically.


  Results Top


Cases were 27 (62.8%) males and 16 (37.2%) females; their mean age ranged between 5 and 75 years) with a mean ± SD age of 31.84 ± 11.429. Controls were 24 (60%) males and 16 (40%) females; their age ranged from 6 to 57 years with a mean ± SD age of 31.33 ± 11.630 [Table 1].
Table 1: Comparative demographic characteristics of alopecia patients and controls

Click here to view


Clinical data of the studied cases in [Table 2].
Table 2: Clinical characteristics of alopecia patients (n=43)

Click here to view


The result of the Mann–Whitney test (U) showed that there was no significant difference between AA patients and controls regarding their serum HSP70 level (ng/ml) (U = 0.502 and P = 0.616) [Table 3].
Table 3: Comparative serum heat shock protein 70 of alopecia patients and controls (n=43)

Click here to view


To correlate between HSP70 and clinical data of AA, Spearman coefficient (rs) was used. The result showed that there was no significant correlation between serum HSP70 and age of patients, disease duration and its SALT score (U = 0.159, 0.292, −0.059 and P > 0.05).

However, there was significant negative correlation between serum HSP70 and AAPI (rs=−0.386 and P = 0.017) [Table 4].
Table 4: Correlation between heat shock protein 70 and clinical data of alopecia areata

Click here to view


Regarding the relation between HSP70 and clinical data of studied cases, there was no significant relation between HSP70 and sex, family history, recurrence, course, site, pattern, nail changes, activity, and SALT score (P > 0.05) [Table 5].
Table 5: Relation between serum heat shock protein 70 and clinical data of alopecia areata

Click here to view



  Discussion Top


AA is among the most highly prevalent human autoimmune disease, leading to disfiguring hair loss due to the collapse of immune privilege of the hair follicle and subsequent autoimmune attack. The genetic basis of AA is largely unknown[7].

AA affects about 5.3 million people worldwide, including males and females across all ethnic groups, with a lifetime risk of 1.7%[8].

Autoimmunity develops against the hair follicle, resulting in nonscarring hair loss that may begin as patches that can coalesce and progress to cover the entire scalp (alopecia totalis) or eventually the entire body (alopecia universalis)[9].

HSPs exist in normal cells and prevent the creation of inappropriate spatial structure caused by inappropriate protein gathering, but due to biological stress and increased toxic and inflammatory chemicals, it is useful in protecting cells from stress[10].

The HSP70 family is the most sensitive group of these proteins and has the most protected structure. HSP70 is a protein that binds to ATP and is found in 60–80% of the eukaryotic cells[11].

The expression of HSP70 is highly upregulated upon a large variety of stress stimuli including thermal stress, anoxia, ethanol, heavy metals, inflammation, infection, and tissue injury[12]. Depending on its intracellular or extracellular location, HSP70 fulfils different functions. Intracellular HSP70 protects cells against lethal damage induced by stress, supports the synthesis and transport of other proteins, and prevents misfolding and aggregation. Extracellular and cell surface-bound HSP70 plays an essential role in eliciting immune responses[6].

Since inflammatory and immune factors play a role in the pathogenesis of AA, we decided to study the association between the serum level of HSP70 (as a systemic inflammatory marker) and the pathogenesis of AA, so this study was designed to evaluate the serum level of HSP70 in AA patients, and its relation to its pathogenesis.

In the current study, among patients, serum HSP70 ranged between 3 and 135 ng/ml with a mean of 22.45 ± 25.916, while in controls, it ranged between 4 and 106 ng/ml with a mean of 21.47 ± 24.315, with no significant difference between AA patients and controls regarding their serum HSP70 level, which disagreed with the Ghaderi[11] study in which 50 individuals with AA and 50 healthy individuals were recruited, then the serum levels of HSP70 were measured, they stated that plasma levels of HSP70 were significantly different between patients with AA and healthy people as plasma levels of HSP70 were significantly higher in patients with AA compared with healthy participants.

On the other hand, in the Thanomkitti et al.[13] study 10 newly diagnosed patchy AA patients (seven males and three females, aged 41.2 ± 7.6 years) with a single lesion (to ensure the homogeneity of the disease spectrum) were enrolled. Among them, 20% had a positive family history of AA. Histopathology confirmed the diagnosis of AA with reduced but still detectable hair follicles underneath without signs of fibrosis or chronicity. They found that HSP70 had a decreased level in patients with AA.

In the current study, there was no significant relation between HSP70 and age of patients, sex, disease duration, family history recurrence, course, site, pattern, nail changes, activity, and SALT score; however, there was significant negative correlation between serum HSP70 and AAPI, but this was in agreement with the Ghaderi[11] study regarding the activity of AA, in which the mean serum level of HSP70 in patients with AA was 64.57% in the acute phase and 59.21% in the chronic phase, but this difference was not statistically significant. On the other hand, this disagreed with the Ghaderi[11] study regarding the pattern and form of AA, where the mean serum level of HSP70 in the localized form was 45.93 and in the diffused form was 85.58, which was statistically significant. The mean serum level of HSP70 in mild, moderate, and severe forms was 45.93, 87.66, and 81.72 which was statistically significant.

Significant elevation plasma levels of HSP70 in other autoimmune diseases such as inflammatory bowel disease, rheumatoid arthritis, and vitiligo were reported by Samborski and Grzymisławski[14] and Abdou et al.[15].

Due to the inflammatory process of AA, which is associated with the accumulation of self-reactive lymphocytes and increased HSP70 in other inflammatory diseases, such as rheumatoid arthritis, as an inflammatory disease vitiligo is similar to AA in its pathogenesis.[16] It can be concluded that HSP70 can be used to diagnose and treat AA and as a marker in the active form of the disease.

HSP70 levels were measured by another method than our method. Also different sample size and characteristics could possibly explain the difference in results.


  Conclusion Top


There was no significant difference between AA patients and controls regarding their serum HSP70 level. So, future research and large-scale studies on different population and ethnicities are needed for a firmer conclusion.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Strazzulla LC, Wang EH, Avila L, Sicco KL, Brinster N, Christiano AM, Shapiro J. Alopecia areata: disease characteristics, clinical evaluation, and new perspectives on pathogenesis. J Am Acad Dermatol 2018; 78:1–2.  Back to cited text no. 1
    
2.
McElwee KJ, Tobin DJ, Bystryn JC, King Jr LE, Sundberg JP. Alopecia areata: an autoimmune disease? Exp Dermatol 1999; 8:371–379.  Back to cited text no. 2
    
3.
Zhang Z, Wang X, Zhang R. Pathogenesis of alopecia areata based on bioinformatics analysis. Indian J Dermatol 2019; 64:1–6.  Back to cited text no. 3
    
4.
Suzuki T, Kumamoto H, Ooya K, Motegi K. Expression of inducible nitric oxide synthase and heat shock proteins in periapical inflammatory lesions. J Oral Pathol Med 2002; 31:488–493.  Back to cited text no. 4
    
5.
Paul MK, Mukhopadhy AK. Tyrosin kinase-role and significance in cancer. Int J Med Sci 2004; 1:101–115.  Back to cited text no. 5
    
6.
Daugaard M, Rohde M, Jäättelä M. The heat shock protein 70 family: highly homologous proteins with overlapping and distinct functions. FEBS Lett 2007; 581:3702–3710.  Back to cited text no. 6
    
7.
Pratt CH, King LE, Messenger AG, Christiano AM, Sundberg JP. Alopecia areata. Nat Rev Dis Primers 2017; 3:1–7.  Back to cited text no. 7
    
8.
Islam N, Leung PS, Huntley AC, Gershwin ME. The autoimmune basis of alopecia areata: a comprehensive review. Autoimmun Rev 2015; 14:81–89.  Back to cited text no. 8
    
9.
Petukhova L, Duvic M, Hordinsky M, Norris D, Price V, Shimomura Y, et al. Genome-wide association study in alopecia areata implicates both innate and adaptive immunity. Nature 2010; 466:113–117.  Back to cited text no. 9
    
10.
Leonardi R, Caltabiano M, Cascone P, Loreto C. Expression of heat shock protein 27 (HSP27) in human temporomandibular joint discs of patients with internal derangement. J Craniofac Surg 2002; 13:713–717.  Back to cited text no. 10
    
11.
Ghaderi R. A novel marker in patients with alopecia areata. MOJ Immunol 2018; 6:311–314.  Back to cited text no. 11
    
12.
Sevin M, Girodon F, Garrido C, De Thonel A. HSP90 and HSP70: implication in inflammation processes and therapeutic approaches for myeloproliferative neoplasms. Mediators Inflamm 2015; 2015:20–25.  Back to cited text no. 12
    
13.
Thanomkitti K, Kanlaya R, Fong-Ngern K, Kapincharanon C, Sueksakit K, Chanchaem P, et al. Differential proteomics of lesional vs. non-lesional biopsies revealed non-immune mechanisms of alopecia areata. Sci Rep 2018; 8:1–3.  Back to cited text no. 13
    
14.
Samborski P, Grzymisławski M. The role of HSP70 heat shock proteins in the pathogenesis and treatment of inflammatory bowel diseases. Adv Clin Exp Med 2015; 24:525–530.  Back to cited text no. 14
    
15.
Abdou AG, Maraee AH, Reyad W. Immunohistochemical expression of heat shock protein 70 in vitiligo. Ann Diagn Pathol 2013; 17:245–249.  Back to cited text no. 15
    
16.
Sandoval-Cruz M, García-Carrasco M, Sánchez-Porras R, Mendoza-Pinto C, Jiménez-Hernández M, Munguía-Realpozo P, Ruiz-Argüelles A. Immunopathogenesis of vitiligo. Autoimmun Rev 2011; 10:762–765.  Back to cited text no. 16
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Patients and methods
Results
Discussion
Conclusion
References
Article Tables

 Article Access Statistics
    Viewed426    
    Printed32    
    Emailed0    
    PDF Downloaded52    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]