Preformed vs de novo anti-human leukocyte antigens-DQ antibodies in kidney transplantation: A retrospective study

Table 1 Immunological and clinical overview of patients with de novo anti-human leukocyte antigen-DQ donor-specific antibodies

Clinical case	Sex	Age	Graft origin/relationship/transplantation date	HLA typing	Immunizing events	Crossmatch	Post-transplant antibodies to HLA I/II	Rejection diagnosis
1	Male	52	LD/spouse/transplanted in 2013	R: A*23/A*33; B*15/B*44; DRB1*01/DRB1*15; DQB1: NT	None: Not immunized pre-transplant	Negative	3 years post TR: Only DSA anti HLA-DQ de novo; DQB1*02:01 ==> MFI 9581; DQB1*03:01 ==> MFI 6962	Proven humoral rejection (biopsy)
				D: A*01/A*02; B*07/B*08; DRB1*03/NT; DQB1*02/DQB1*03
2	Male	49	LD/mother/transplanted in 2014	R: A*02/NT; B*38/B*52; DRB1*08/DRB1*15; DQB1*06/DQB1*06	None: Not immunized pre-transplant	Negative	3 years post TR: Only DSA anti HLA-DQ de novo; DQB1*02:01 ==> MFI 16317; DQB1*02:02 ==> MFI 14917	Proven humoral rejection (biopsy)
				D: A*02/A*29; B*38/B*45; DRB1*08/DRB1*09; DQB1*02/DQB1*06
3	Female	25	LD/mother/transplanted in 2013	R: A*03/A*68; B*14/NT; DRB1*11/DRB1*11; DQB1*03/NT	2 transfusions: Not immunized pre-transplant	Negative	6 years post TR: DSA anti HLA-DQ de novo; DQB1*03:02 ==> MFI 19473; DQB1*03:03 ==> MFI 8663 Associated with DSA A2 ==> MFI 7004	Proven humoral rejection (biopsy)
				D: A*02/A*68; B*14/B*21; DRB1*07/DRB1*11; DQB1*03/NT
4	Male	40	LD/spouse/transplanted in December 2025	R: A*24/A*29; B*44/B*50; DRB1*15/DRB1*15; DQB1*06/DQB1*06	None: DSA anti DR4 (MFI 123)	Negative	4 years post TR: Only DSA anti HLA-DQ de novo; MFI 10189 < DQB1*02 < MFI 12029	Proven humoral rejection (biopsy)
				D: A*01/A*02; B*08/B*18; DRB1*03/DRB1*04; DQB1*02/DQB1*04
5	Male	55	LD/sister/transplanted in 2016	R: A*68/NT; B*18/NT; DRB1*02/NT; DQB1*02/NT	None: Not immunized pre-transplant	Negative	17 months post TR: DSA anti HLA-DQ de novo; DQB1*06 ==> MFI 17963 Associated with: MFI 4870 < DSA A*66 < MFI 14271; DSA B*27 ==> MFI 19112	Proven humoral rejection (biopsy)
				D: A*68/A*66; B*18/B*27; DRB1*03/DRB1*15; DQB1*02/DQB1*06
6	Female	54	LD /sister/transplanted in November 2016	R: A*01/A*02; B*07/B*50; DRB1*03/NT; DQB1: NT	2 transfusions/2 pregnancies: A32 (MFI 1600), DR16 (MFI 1103)	Negative	6 months post TR: Only DSA anti HLA-DQ de novo; DQA1*05:01 ==> MFI 599	Suspicion of humoral rejection
				D: A*24/A*30; B*13/B*51; DRB1*07/DRB1*11; DQB1*02/DQB1*03; DQA1*02/DQA1*05

LD: Living donor; NT: Not typed; TR: Kidney transplantation; DSA: Donor-specific antibody; HLA: Human leukocyte antigen; MFI: Median fluorescence intensity.

Table 2 Histological results of serial renal allograft biopsies in case 4, according to the Banff classification

Date (post-transplant)	Glomerulitis	Interstitial inflammation	Tubulitis	Intimal arteritis	Chronic glomerulopathy	Mesangial matrix expansion	Total interstitial inflammation	Interstitial fibrosis	Tubular atrophy	Vascular intimal fibrous thickening	Peritubular capillaritis	Other parenchymal tubular lesions	Arteriolar hyalinosis	C4d	Conclusion
January 2016 (day 11)	0	0	0	0	0	0	0	NR	0	0	NR	0	0	Negative	Isolated tubular epithelial lesion
April 2019 (4 years)	0	0	0	0	0	0	NR	1	1	0	3	NR	1	Positive	Active ABMR
January 2020 (5 years)	0	0	0	0	0	0	0	1	1	0	2	NR	2	Positive (focal)	Active ABMR

0: Lesion evaluated and absent; 1: Mild; 2: Moderate; 3: Severe; NR: Not reported; C4d: Complement component 4d; ABMR: Antibody-mediated rejection.

Table 3 Histological results of serial renal allograft biopsies in case 6, according to the Banff classification

Date (post-transplant)	Glomerulitis	Interstitial inflammation	Tubulitis	Intimal arteritis	Chronic glomerulopathy	Mesangial matrix expansion	Interstitial fibrosis	Tubular atrophy	Vascular intimal fibrous thickening	Peritubular capillaritis	Arteriolar hyalinosis	C4d	Conclusion
December 2016 (day 33)	0	0	0	0	0	0	0	0	0	0	1	Positive	Acute tubular necrosis with C4d positivity (suspicion of AMR)
May 2017 (6 months)	1	0	0	0	0	0	1	1	0	0	1	Positive	Mild IFTA with arteriolar hyalinosis, no rejection

0: Lesion evaluated and absent; 1: Mild; C4d: Complement component 4d; AMR: Antibody-mediated rejection; IFTA: Interstitial fibrosis and tubular atrophy.