Immunologic clustering of donor-specific antibodies and clinical outcomes in kidney transplant recipients

doi:10.5500/wjt.v16.i2.118450

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World Journal of Transplantation

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2220-3230

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Retrospective Study

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Transplant. Jun 18, 2026; 16(2): 118450
Published online Jun 18, 2026. doi: 10.5500/wjt.v16.i2.118450

Table 1 Patient demographics and baseline characteristics

Variable	Category	n (%)
Recipient gender	Female	54 (48.2)
	Male	58 (51.8)
Donor gender	Female	35 (31.2)
	Male	77 (68.8)
Donor type	Deceased	8 (7.1)
	Living	104 (92.9)
DSA presence	Present	112 (100.0)
Induction therapy	ATG only	108 (96.4)
	Basiliximab only	4 (3.6)
Sensitizing events	None	103 (92.0)
	Pregnancy	5 (4.5)
	Blood Transfusion	4 (3.5)
Maintenance therapy	CSA + MMF + PRED	1 (0.9)
	FK + MMF + PRED	111 (99.1)
Pre-transplant desensitization	No	60 (53.6)
	Yes	52 (46.4)
Previous transplant	No	109 (97.3)
	Yes	3 (2.7)
IVIG use	No	45 (40.2)
	Yes	67 (59.8)
Variable	Median	IQR/unit
Recipient age (years)	46.0	35.0-60.0
Donor age (years)	35.0	29.0-43.2
ATG dose (mg/kg)	5.0	4.0-5.0
Length of stay (days)	9.0	8.0-12.0
Creatinine-4 months (μmol/L)	90.0	72.0-112.0
Creatinine-1 year (μmol/L)	83.0	72.5-107.0
Creatinine-2 years (μmol/L)	82.0	69.2-104.5
eGFR-4 months (mL/minute)	78.0	62.5-96.2
eGFR-1 year (mL/minute)	86.0	67.0-99.5
eGFR-2 years (mL/minute)	86.5	72.5-102.0

DSA: Donor-specific antibody; ATG: Anti-thymocyte globulin; CSA: Cyclosporine A; FK: Tacrolimus; MMF: Mycophenolate mofetil; PRED: Prednisolone; IVIG: Intravenous immunoglobulin; eGFR: Estimated glomerular filtration rate; IQR: Interquartile range.

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Table 2 Clinical interpretation and labeling of the three clusters based on immunologic and outcome profiles

Cluster	Immunologic profile	Risk interpretation	Key characteristics
0	Combined Class I + II sensitization	High risk	Highest DSA number, high MFI, broad reactivity, highest rejection/mortality
1	Predominantly Class II sensitization	Intermediate risk	Moderate MFI, mild graft loss/mortality, no acute rejection
2	Class I only sensitization	Low risk	Low MFI, low DSA number, no graft loss or mortality

K-means clustering completed with 3 clusters, in a total of 112. Cluster 0 had 58 patients. Cluster 1 had 34 patients. Cluster 2 had 20 patients. DSA: Donor-specific antibody; MFI: Mean fluorescence intensity.

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Table 3 Patient demographics and baseline characteristics by cluster

Risk group	Variable	Category	n (%)
Categorical variables
High risk	Recipient gender	Male	30 (51.7)
		Female	28 (48.3)
	Donor gender	Male	37 (63.8)
		Female	21 (36.2)
	Donor type	Living	52 (89.7)
		Deceased	6 (10.3)
Intermediate risk	Recipient gender	Male	17 (50.0)
		Female	17 (50.0)
	Donor gender	Male	27 (79.4)
		Female	7 (20.6)
	Donor type	Living	33 (97.1)
		Deceased	1 (2.9)
Low risk	Recipient gender	Male	11 (55.0)
		Female	9 (45.0)
	Donor gender	Male	13 (65.0)
		Female	7 (35.0)
	Donor type	Living	19 (95.0)
		Deceased	1 (5.0)
High risk	DSA presence	Present	58 (100.0)
	Induction therapy	ATG only	58 (100.0)
	Sensitizing events	None	53 (91.4)
		Pregnancy	3 (5.2)
		Blood transfusion	2 (3.4)
Intermediate risk	DSA presence	Present	34 (100.0)
	Induction therapy	ATG only	31 (91.2)
		Basiliximab only	3 (8.8)
	Sensitizing events	None	31 (91.2)
		Pregnancy	3 (8.8)
Low risk	DSA presence	Present	20 (100.0)
	Induction therapy	ATG only	19 (95.0)
		Basiliximab only	1 (5.0)
	Sensitizing events	None	19 (95.0)
		Blood Transfusion	1 (5.0)
High risk	Maintenance therapy	FK + MMF + PRED	57 (98.3)
		CSA + MMF + PRED	1 (1.7)
	Diabetes pre-transplant	No	31 (53.4)
		Yes	27 (46.6)
	Previous transplant	No	56 (96.6)
		Yes	2 (3.2)
	IVIG use	No	18 (31.0)
		Yes	40 (69.0)
Intermediate risk	Maintenance therapy	FK + MMF + PRED	34 (100.0)
	Diabetes pre-transplant	No	16 (47.1)
		Yes	18 (52.9)
	Previous transplant	No	34 (100.0)
	IVIG use	No	15 (44.1)
		Yes	19 (55.9)
Low risk	Maintenance therapy	FK + MMF + PRED	20 (100.0)
	Diabetes pre-transplant	No	13 (65.0)
		Yes	7 (35.0)
	Previous transplant	No	19 (95.0)
		Yes	1 (5.0)
	IVIG use	No	12 (60.0)
		Yes	8 (40.0)
High risk	Acute rejection	No	54 (93.1)
		Yes	4 (6.9)
	Graft loss	No	54 (93.1)
		Yes	4 (6.9)
	Delayed graft function	No	56 (96.6)
		Yes	2 (3.4)
	Mortality	No	55 (94.8)
		Yes	3 (5.2)
	CMV infection	No	56 (96.6)
		Yes	2 (3.4)
	BKV infection	No	54 (98.2)
		Yes	1 (1.8)
Intermediate risk	Acute rejection	No	34 (100.0)
	Graft loss	No	32 (94.1)
		Yes	2 (5.9)
	Delayed graft function	No	32 (94.1)
		Yes	2 (5.9)
	Mortality	No	32 (94.1)
		Yes	2 (5.9)
	CMV infection	No	33 (97.1)
		Yes	1 (2.9)
	BKV infection	No	29 (96.7)
		Yes	1 (3.3)
Low risk	Acute rejection	No	19 (95.0)
		Yes	1 (5.0)
	Graft loss	No	20 (100.0)
	Delayed graft function	No	20 (100.0)
	Mortality	No	20 (100.0)
	CMV infection	No	20 (100.0)
	BKV infection	No	19 (100.0)
Continuous variables
Risk group	Variable	Median	IQR/unit
High risk (years)	Recipient age	46.5	31.5-59.8
High risk (years)	Donor age	35.5	29.0-44.0
Intermediate risk (years)	Recipient age	51.5	39.5-62.8
Intermediate risk (years)	Donor age	35	29.0-43.2
Low risk (years)	Recipient age	42.5	36.5-52.8
Low risk (years)	Donor age	32.5	27.2-39.2
High risk
	Length of stay (days)	9	8.0-12.0
	Creatinine 4 months (μmol/L)	94	76.0-114.0
	eGFR 4 months (mL/minute)	76.5	63.2-88.0
Intermediate risk
	Length of stay (days)	10	8.0-11.0
	Creatinine 4 months (μmol/L)	88	70.5-110.8
	eGFR 4 months (mL/minute)	78	59.5-97.5
Low risk	Length of stay (days)	9	7.0-12.5
	Creatinine 4 months (μmol/L)	77.5	69.8-103.8
	eGFR 4 months (mL/minute)	92	66.2-109.5

DSA: Donor-specific antibody; ATG: Anti-thymocyte globulin; FK: Tacrolimus; MMF: Mycophenolate mofetil; CSA: Cyclosporine A; PRED: Prednisolone; IVIG: Intravenous immunoglobulin; eGFR: Estimated glomerular filtration rate; IQR: Interquartile range; LOS: Length of stay; AR: Acute rejection; DGF: Delayed graft function; CMV: Cytomegalovirus; BKV: BK virus.

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Table 4 Comparison of cluster features (univariate analysis), n (%)

Variable	High risk (n = 58)	Intermediate risk (n = 34)	Low risk (n = 20)	P value	Significance
Donor and recipient
Recipient gender				0.9388	Not significant
Male	30 (51.7)	17 (50.0)	11 (55.0)
Female	28 (48.3)	17 (50.0)	9 (45.0)
Recipient age, median (IQR)	46.5 (31.5-59.8)	51.5 (39.5-2.8)	42.5 (36.5-52.8)	0.1989	Not significant
Donor gender				0.2735	Not significant
Male	37 (63.8)	27 (79.4)	13 (65.0)
Female	21 (36.2)	7 (20.6)	7 (35.0)
Donor age, median (IQR)	35.5 (29.0-44.0)	35.0 (29.0-43.2)	32.5 (27.2-39.2)	0.3195	Not significant
Donor type				0.3791	Not significant
Living donor	52 (89.7)	33 (97.1)	19 (95.0)
Deceased donor	6 (10.3)	1 (2.9)	1 (5.0)
DSA and HLA matching
HLA mismatches, median (IQR)	8.0 (6.2-10.0)	6.0 (5.0-7.0)	7.0 (5.0-9.0)	0.0000	Significant
DSA type	Class I + II, 58 (100.0)	Class II only, 34 (100.0)	Class I, 19 (95.0), Class II, 1 (5.0)	-	Not tested
Number of DSAs, median (IQR)	5.0 (2.0-7.8)	3.0 (2.0-6.0)	1.0 (1.0-2.2)	0.0005	Significant
Cumulative DSA strength (MFI), median (IQR)	3811.0 (2366.5-6998.8)	2277.0 (1213.8-3900.8)	686.5 (612.5-857.5)	0.0000	Significant
Treatment and sensitization
Sensitizing events
Sensitized	5 (8.6)	3 (8.8)	1 (5.0)	1.0000	Not significant
Not sensitized	53 (91.4)	31 (91.2)	19 (95.0)	1.0000	Not significant
Induction therapy
ATG	58 (100.0)	31 (91.2)	19 (95.0)	0.0825	Borderline
Basiliximab	0 (0.0)	3 (8.8)	1 (5.0)	0.0825	Borderline
Maintenance therapy
FK MMF PRED	57 (98.3)	34 (100.0)	20 (100.0)	0.6252	Not significant
CSA MMF PRED	1 (1.7)	0 (0.0)	0 (0.0)	0.6252	Not significant
Diabetes pre-transplant
Yes	27 (46.6)	18 (52.9)	7 (35.0)	0.4426	Not significant
No	31 (53.4)	16 (47.1)	13 (65.0)	0.4426	Not significant
Previous transplant
Yes	2 (3.4)	0 (0.0)	1 (5.0)	-	Not tested
No	56 (96.6)	4 (100.0)	19 (95.0)	-	Not tested
IVIG use
Yes	40 (69.0)	19 (55.9)	8 (40.0)	0.0637	Borderline
No	18 (31.0)	15 (44.1)	12 (60.0)	0.0637	Borderline
ATG dose	5.0 (4.0-5.0)	5.0 (4.0-5.0)	5.0 (4.0-5.0)	0.7762	Not significant
Graft function and outcomes
Acute rejection
Yes	4 (6.9)	0 (0.0)	1 (5.0)	0.3002	Not significant
No	54 (93.1)	20 (100.0)	19 (95.0)	0.3002	Not significant
Graft loss
Yes	4 (6.9)	2 (5.9)	0 (0.0)	0.4912	Not significant
No	54 (93.1)	32 (94.1)	20 (100.0)	0.4912	Not significant
Delayed graft function				0.5298	Not significant
Yes	2 (3.4)	2 (5.9)	0 (0.0)
No	56 (96.6)	32 (94.1)	20 (100.0)
Death (mortality)
Yes	3 (5.2)	2 (5.9)	0 (0.0)	0.5590	Not significant
No	55 (94.8)	32 (94.1)	20 (100.0)
CMV infection
Yes	2 (3.4)	1 (2.9)	0 (0.0)	0.7078	Not significant
No	56 (96.6)	19 (97.1)	20 (100.0)	0.7078	Not significant
BKV infection
Yes	1 (1.8)	1 (3.3)	0 (0.0)	-	Not tested
No	54 (98.2)	29 (96.7)	19 (100.0)	-	Not tested
Length of stay (days)	9.0 (8.0-12.0)	10.0 (8.0-11.0)	9.0 (7.0-12.5)	0.9692	Not significant
Creatinine at 4 months (µmol/L)	94.0 (76.0-114.0)	88.0 (70.5-110.8)	77.5 (69.8-103.8)	0.4911	Not significant
eGFR at 4 months (mL/minute/1.73 m²)	76.0 (64.0-88.0)	78.0 (59.5-97.5)	92.0 (66.2-109.5)	0.3234	Not significant

P value < 0.05 was considered statistically significant. Continuous variables were analyzed using the Kruskal-Wallis test, and categorical variables were assessed using the χ² test as appropriate, based on expected cell counts. DSA: Donor-specific antibody; HLA: Human leukocyte antigen; ATG: Anti-thymocyte globulin; FK: Tacrolimus; MMF: Mycophenolate mofetil; CSA: Cyclosporine A; PRED: Prednisolone; IVIG: Intravenous immunoglobulin; eGFR: Estimated glomerular filtration rate; MFI: Mean fluorescence intensity; CMV: Cytomegalovirus; IQR: Interquartile range; BKV: BK virus.

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Table 5 Immunologic stratification and antibody patterns by risk cluster (median values)

Risk cluster	Class I MFI	Class II MFI	eGFR at 4 months (mL/minute/1.73 m²)	HLA mismatches	DSA type	DSA count
High risk cluster	1174	1966	76	8	Both	5
Intermediate risk cluster	0	2277	78	6	Class II	3
Low risk cluster	686	0	92	7	Class I	1

MFI: Mean fluorescence intensity; eGFR: Estimated glomerular filtration rate; HLA: Human leukocyte antigen; DSA: Donor-specific antibody.

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Table 6 Frequency (and percentage) of key adverse clinical outcomes observed within each immunologic risk cluster, n (%)

Cluster	Acute rejection	Graft loss	Delayed graft function	Mortality
High risk cluster	4 (6.9)	4 (6.9)	2 (3.4)	3 (5.2)
Intermediate risk	0 (0.0)	2 (5.9)	2 (5.9)	2 (5.9)
Low risk cluster	1 (5.0)	0 (0.0)	0 (0.0)	0 (0.0)

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Citation: Al-Qurashi SH, Khalil MAM, Mahmood HHK, Alsharif MM, Alqurashi YF, Alghamdi L, Al-Ghamdi RA, Alsaedi ZA, Cruz AJD, Aboasamh GA, Sadagah NM. Immunologic clustering of donor-specific antibodies and clinical outcomes in kidney transplant recipients. World J Transplant 2026; 16(2): 118450
URL: https://www.wjgnet.com/2220-3230/full/v16/i2/118450.htm
DOI: https://dx.doi.org/10.5500/wjt.v16.i2.118450

Al-Qurashi SH, Khalil MAM, Mahmood HHK, Alsharif MM, Alqurashi YF, Alghamdi L, Al-Ghamdi RA, Alsaedi ZA, Cruz AJD, Aboasamh GA, Sadagah NM. Immunologic clustering of donor-specific antibodies and clinical outcomes in kidney transplant recipients. World J Transplant 2026; 16(2): 118450 [DOI: 10.5500/wjt.v16.i2.118450]

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