Effect of serial plasma exchange sessions with albumin replacement on ABO antibody titers

Mohamed S Hassan; Mahmoud M Zaki; Tamer W El Said; Haitham E Abdelaziz; Mahmoud S M Al-Semrawy; Hebatallah N Elsayed; Shaimaa Z Abdelmegied

doi:10.4103/ejh.ejh_28_22

ORIGINAL ARTICLE

Year : 2022 | Volume : 47 | Issue : 3 | Page : 217-221

Effect of serial plasma exchange sessions with albumin replacement on ABO antibody titers

Mohamed S Hassan¹, Mahmoud M Zaki¹, Tamer W El Said¹, Haitham E Abdelaziz¹, Mahmoud S M Al-Semrawy², Hebatallah N Elsayed³, Shaimaa Z Abdelmegied¹
¹ Department of Nephrology, Ain Shams University, Cairo, Egypt
² Department of Clinical Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
³ Department of Nephrology, Nile Badrawi Hospital, Cairo, Egypt

Date of Submission	04-May-2022
Date of Acceptance	10-May-2022
Date of Web Publication	03-Jan-2023

Correspondence Address:
Mahmoud S M Al-Semrawy
Samanoud, MSC, Gharbia
Egypt

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/ejh.ejh_28_22

Abstract

Background Donor shortage in kidney transplantation stimulates trails of live-related transplants across the ABO antibody barrier. Successful desensitization was achieved by repeated plasmapheresis with intensified immunosuppression. This study estimates the effect of serial sessions of plasma exchange on different blood group antibody titers. Patients and methods This is a pilot study that included 25 prescribed plasma exchange treatments with albumin replacement for miscellaneous indications. Patients using plasma as a replacement during sessions, positive direct and indirect antiglobulin test and AB blood group were excluded. Blood group antibody titers were measured by the gel card method before starting plasma exchange and after each session for five sessions. Results The study included a total of 25 patients, 12 (48%) had A1 blood group, eight (32%) had blood group B, and five (20%) had blood group O. The baseline anti-(A) and anti-(B) antibody titers before plasma exchange were median (interquartile range) 128.00 (192) and 64 (64) with significant reduction after five sessions with median (interquartile range) 1 (4) and 2 (1), respectively, with P value less than 0.001. Anti-(A) and anti-(B) antibody titer percent reduction from baseline to fifth session were mean±SD=99.04 ± 0.72 and =97.93 ± 0.99%, respectively. Anti-(A) and anti-(B) antibody titers were negatively correlated with patient’s age (r=0.731, P=0.005; r=0.793, P<0.001, respectively). Patients with age less than 50 (n=13) years have higher anti-(A) and anti-(B) antibodies compared with patients with age more than 50 years (N=12) with P value less than 0.001. Also, on comparing patients on immunosuppressive drugs with patients not on immunosuppressive drugs as regards baseline antibody titers before exchange sessions and after five plasma exchange sessions, there was no significant difference in anti-(B) while anti-(A) titer was higher in patients without immunosuppressive drugs with P valueless than 0.05 and on fifth session, P value of 0.01. Conclusion Serial plasma exchange sessions with albumin replacement is an effective method for ABO antibody titer reduction. Baseline titers seem to be affected by age and adjuvant immunosuppressive therapy.

Keywords: ABO antibody titers, plasma exchange, transplantation

How to cite this article:
Hassan MS, Zaki MM, El Said TW, Abdelaziz HE, Al-Semrawy MS, Elsayed HN, Abdelmegied SZ. Effect of serial plasma exchange sessions with albumin replacement on ABO antibody titers. Egypt J Haematol 2022;47:217-21

How to cite this URL:
Hassan MS, Zaki MM, El Said TW, Abdelaziz HE, Al-Semrawy MS, Elsayed HN, Abdelmegied SZ. Effect of serial plasma exchange sessions with albumin replacement on ABO antibody titers. Egypt J Haematol [serial online] 2022 [cited 2023 Mar 30];47:217-21. Available from: http://www.ehj.eg.net/text.asp?2022/47/3/217/366864

Introduction

The most effective treatment of end-stage renal disease is kidney transplantation, but donor shortage has significantly limited this treatment. This problem is even more in countries with poor deceased donor transplant programs and predominantly living-related donor transplant programs. To overcome this profound donor shortage, immunological barriers historically considered as absolute contraindications to transplantation are being reevaluated. One such barrier is the ABO blood group incompatibility [1]. Kidney transplantation is best performed in the absence of (major) ABO incompatibility, a large end-stage kidney disease population, and an increasing organ shortage result in waiting times for a deceased donor kidney transplant exceeding 5 years in some countries such as Germany. One possibility to reduce the waiting time is the transplantation across ABO antibody barriers. Theoretically, the number of kidney transplantations from living donors can be increased by up to 30% when patients are transplanted across the ABO antibody barrier [2]. With currently existing protocols, as many as 90% of patients with an ABOi living donor may effectively be desensitized and transplanted. The aim of desensitization protocols is the reduction and maintenance of anti-A/B antibodies during the first 2 weeks after transplantation below a threshold that is considered to be safe. Thereafter, even when anti-(A/B) antibodies recur at high levels they will not harm the kidney transplant, a phenomenon called accommodation. In recent years, graft survival rates after ABOi kidney transplantation nearly equaled those after ABO-compatible procedures [2].

Aim

This study demonstrates the effect of serial sessions of plasma exchange with albumin replacement on ABO antibody titers.

Patients and methods

This is a prospective cohort study that enrolled 25 patients on therapeutic plasma exchange sessions for at least five sessions at Ain Shams University Hospitals. Patients with blood group AB, patients with positive direct and indirect antiglobulin tests for autoantibodies, and those on plasma exchange sessions using plasma as a replacement fluid were excluded. All patients underwent therapeutic plasma exchange sessions for five sessions. All patients were subjected to informed consent, detailed history taking, full clinical examination, as well as laboratory investigations, including blood grouping, Coombs test (direct and indirect), and anti-(A/B) antibody titers, which were measured before plasma exchange and after each session for five sessions using the gel card method. The protocol was approved by the ethics committee of our institution before the study began, and it conformed to the ethical guidelines of the 1964 Helsinki Declaration.

Gel card method

Titration of ABO antibodies is usually performed with serial two-fold dilutions of serum with selected red cells. Titration values can provide information on the relative amount of antibodies present in the serum, and this information is especially important in cases of ABOi solid organ transplantations [3].

Statistical analysis

Data were collected, revised, coded, and entered into the Statistical Package for the Social Sciences, version 20 (SPSS Inc., Chicago, Illinois, USA). The qualitative data were presented as numbers and percentages, whereas quantitative data were presented as mean with SD or median with interquartile ranges (IQR) for nonparametric data. Comparison between two groups with qualitative data was done using the χ² test. Comparison between two groups with quantitative data was done by the two-tailed independent t test when the distribution of the data was found parametric. Mann–Whitney test was used with the nonparametric data. Pearson’s correlation coefficients were used to assess the correlations.

The P value was considered significant as follows:

P value more than 0.05: nonsignificant.

P value less than 0.05: significant.

P value less than 0.01: highly significant.

Results

[Table 1] shows that the study included a total of 25 patients, 16 (64%) men and nine (36%) women with a mean age of 44.24 ± 11.96; 13 patients more than 50 years and 12 patients less than 50 years. Twelve (48%) had A1 blood group, eight (32%) had blood group B, and five (20%) had blood group O. The baseline anti-(A) and anti-(B) antibody titers before plasma exchange were median (IQR) 128 (192) and 64 (64) with significant reduction after five sessions with median (IQR) 1 (4) and 2 (1), respectively, with P value less than 0.001 ([Table 2]). Anti-(A) and Anti-(B) antibody titer percent reduction from baseline to fifth session were mean±SD=99.04 ± 0.72 and 97.9 3 ± 0.99%, respectively ([Table 3]). Anti-(A) and anti-(B) antibody titer were negatively correlated with patient’s age (r=0.731, P=0.005; r=0.793, P<0.001), respectively. Patients with age less than 50 (n=13) years have higher anti-(A) and anti-(B) antibodies compared with patients with age more than 50 years (N=12) with P value less than 0.001 ([Table 4]). Also, on comparing patients on immunosuppressive drugs with patients without as regards baseline antibody titers before exchange sessions and after five plasma exchange sessions, there was no significant difference in anti-(B) while anti-(A) titers were higher in patients without immunosuppressive drugs with P value less than 0.05 and on fifth session, P value of 0.01 ([Table 5]).

Table 1: Demographic data of the studied patients

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Table 2: Effect of plasma exchange on anti-(A/B) antibody titers

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Table 3: Percent change in anti-(A/B) antibody compared with baseline titers

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Table 4: Relation between age group and anti-(A) and anti-(B) antibody titers

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Table 5: Relation between use of immunosuppressive drugs and anti-(A/B) antibody titers

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Discussion

A better understanding of immunological mechanisms and various effective regimens for controlling ABO-I KT is now being performed with increasing frequency [4]. Even in India, there are many centers now performing ABO-I KT. However, the numbers are small, and there are very few published reports from India. For a good outcome, most important is to achieve and maintain low anti-blood group antibody titers [5]. This study demonstrates the effect of serial plasma exchange sessions with albumin replacement on ABO antibody titers.

Our study revealed a statistically significant reduction of anti-(A) and anti-(B) antibody titers after five sessions of plasma exchange using albumin as a replacement fluid. Within the same context, Tydén et al. [6] found that the simplest and most common method to remove antibodies from plasma is therapeutic plasma exchange, in which large amounts of plasma are withdrawn and replaced with colloid solutions. In agreement with our study Thielke et al. [7] showed that several pretransplant apheresis sessions are required for antibody removal before ABOi organ transplantation. Genberg et al. [8] showed that in the field of ABOi KT, currently used antibody depletion techniques include therapeutic plasma exchange, double-filtration plasmapheresis, and antigen-specific immunoadsorption. The great difference among these techniques is their degree of selectivity. Montgomery [9] reported that very close monitoring of the anti-ABO antibody titer is typically carried out for a minimum of 2 weeks. If necessary, plasmapheresis is added to eliminate the rebounding antibody level.

Our study reported that anti-(A/B) antibody titers after five sessions of plasma exchange were 1: 8 or lower. This came in agreement with Takahashi [10], who reported that most centers performing ABOi KT have adhered to the guideline that serum anti-ABO antibody titers should be 1: 16 or lower before transplantation. However, the acceptable upper limit of anti-ABO antibody titers is exclusively based on empirical evidence, not substantiated by deductive reasoning. Wilpert et al. [11] decreased the antibody titer to below 1: 4 before transplant; Chung et al. in 2011 [12] chose a limit of 1: 32 in their preconditioning protocol. Toki et al. [13] reported that the target titers of anti-ABO antibodies immediately before KT in Japan are usually 1: 16 to 1: 32 or less.

Our study revealed that percent reduction of anti-(A) and anti-(B) antibody titers compared with baseline were −99.04 and −97.93%, respectively, after five sessions of plasma exchange and this come in agreement with Tydén et al. [6], who showed that plasma exchange eliminates approximately −20% of the anti-(A/B) antibodies with each session.

Our study reported that anti-(A) and anti-(B) antibody titers in patients older than 50 years were very low compared with titers in patients younger than 50 years and there was a statistically significant negative correlation between age and anti-A and anti-B antibody titers (P<0.005). This is in agreement with Mollison et al. [14], who reported that the ABO antibody titers were believed to be highest in teenagers and decreased with age based on the statement in a famous transfusion medicine textbook. Tendulkar et al. [15], assessed 1635 group O Indian donors (male and female) with serial dilutions for anti-(A) and anti-(B) antibodies. Their study determined that there was an inverse relationship between titer and age in the male group O donors for both anti-(A) and anti-(B). Khampanon et al. [16], tested 300 group O donors (males and females) for anti-(A)and anti-(B) titers through serial dilutions. Their study determined that anti-B titers decreased with age in both males and females. De Franca et al. [17] tested 603 group O Brazilian blood donors (males and females) for anti-(A), anti-(B) titers. This group found men over 50 years had statistically lower titers compared with the younger age groups. Tendulkar et al. [15] showed that the prevalence of high-titer donors was significantly lower in the age groups of 40–49 and 50 years and over when compared with the 16–29 years age group. Although not much-published data exist on this topic, other authors have noted similar trends. On the contrary, Rieben et al. [18] published an article showing no significant decline in agglutinin titers with increasing age. In contrast to our study, Aufder Maur et al. [19] demonstrated that the median anti-ABO antibody titers were elevated in elderly persons of blood group O in 1993.

On comparing patients on immunosuppressive drugs with patients without as regards baseline antibody titers before exchange sessions and after five plasma exchange sessions, there was no significant difference in anti-(B) while anti-(A) titers, which were higher in patients without immunosuppressive drugs with P value less than 0.05 and on fifth session, P value of 0.01. In agreement with our study, Takahashi et al. [20] reported that both patient and graft survival significantly improved in ABOi renal transplantation. This is due to maintenance immunosuppression based on tacrolimus and MMF and the use of rituximab. In contrast to this Chuang et al. [21] showed that maintenance-immunosuppressive therapy did not affect anti-(A/B)titer in ABOi KT.

Conclusion

Serial plasma exchange session with albumin replacement is an effective method for ABO antibody titer reduction. Baseline titers seem to be affected by age and adjuvant immunosuppressive therapy.

Acknowledgements

The authors acknowledge the contributions of individuals in the Nephrology Department of Ain Shams University Hospitals who participated in data preparation and collection in this article.

Author contributions: Mohamed S. Hassan: reading, interpretation, and writing of the manuscript. Mahmoud M Zaki: reading and supervision of the manuscript. Tamer W. El Said: the idea of the research and study design, formulation, interpretation, writing, and revision of the manuscript. Haitham E. Abdelaziz: reading and supervision, revision of the manuscript. Mahmoud S.M. Al-Semrawy: data collection, sampling, reading, and writing of the manuscript. Hebatallah N. Elsayed: reading and interpretation of tests. Shaimaa Z. Abdelmegied: reading, interpretation, writing, and revision of the manuscript.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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