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. 2024 Jun 17;10(2):e004315.
doi: 10.1136/rmdopen-2024-004315.

Predictive utility of ANCA positivity and antigen specificity in the assessment of kidney disease in paediatric-onset small vessel vasculitis

Simranpreet K Mann  1   2 , Jeffrey N Bone  2 , Else S Bosman  3 , David A Cabral  2   3   4 , Kimberly A Morishita  2   3   4 , Kelly L Brown  5   3 ; PedVas Investigator Network
Collaborators, Affiliations

Predictive utility of ANCA positivity and antigen specificity in the assessment of kidney disease in paediatric-onset small vessel vasculitis

Simranpreet K Mann et al. RMD Open. .

Abstract

Objectives: The objective of this study is to evaluate whether anti-neutrophil cytoplasmic antibody (ANCA) seropositivity and antigen specificity at diagnosis have predictive utility in paediatric-onset small vessel vasculitis.

Methods: Children and adolescents with small vessel vasculitis (n=406) stratified according to the absence (n=41) or presence of ANCA for myeloperoxidase (MPO) (n=129) and proteinase-3 (PR3) (n=236) were compared for overall and kidney-specific disease activity at diagnosis and outcomes between 1 and 2 years using retrospective clinical data from the ARChiVe/Paediatric Vasculitis Initiative registry to fit generalised linear models.

Results: Overall disease activity at diagnosis was higher in PR3-ANCA and MPO-ANCA-seropositive individuals compared with ANCA-negative vasculitis. By 1 year, there were no significant differences, based on ANCA positivity or specificity, in the likelihood of achieving inactive disease (~68%), experiencing improvement (≥87%) or acquiring damage (~58%). Similarly, and in contrast to adult-onset ANCA-associated vasculitis, there were no significant differences in the likelihood of having a relapse (~11%) between 1 and 2 years after diagnosis. Relative to PR3-ANCA, MPO-ANCA seropositivity was associated with a higher likelihood of kidney involvement (OR 2.4, 95% CI 1.3 to 4.7, p=0.008) and severe kidney dysfunction (Kidney Disease Improving Global Outcomes (KDIGO) stages 4-5; OR 6.04, 95% CI 2.77 to 13.57, p<0.001) at onset. Nonetheless, MPO-ANCA seropositive individuals were more likely to demonstrate improvement in kidney function (improved KDIGO category) within 1 year of diagnosis than PR3-ANCA seropositive individuals with similarly severe kidney disease at onset (p<0.001).

Conclusions: The results of this study suggest important paediatric-specific differences in the predictive value of ANCA compared with adult patients that should be considered when making treatment decisions in this population.

Keywords: Autoantibodies; Autoimmune Diseases; Autoimmunity; Child; Vasculitis.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
Overall disease activity (pVAS) at diagnosis in paediatric-onset small vessel vasculitis stratified by ANCA status. A linear regression model adjusted for age at the time of diagnosis and sex was used to compare overall disease activity, quantified using the total pVAS (y-axis), at diagnosis in n=398 children and adolescents with small vessel vasculitis (x-axis) stratified according to the absence (ANCA -, n=40) or presence (ANCA +, n=358) of ANCA as well as specificity of ANCA towards MPO (MPO-ANCA, n=126) and PR3 (PR3-ANCA, n=232). Data are presented as boxplots showing the median (solid line) and IQR. See online supplemental table S1 for mean differences. ANCA, anti-neutrophil cytoplasmic antibody; MPO, myeloperoxidase; pVAS, paediatric Vasculitis Activity Score.
Figure 2
Figure 2
Time of diagnosis organ involvement associated with ANCA positivity and specificity. A logistic regression model adjusted for age at the time of diagnosis and sex was used to evaluate differences in organ involvement (y-axis; organ system) at diagnosis between children stratified by ANCA status (ANCA negative, n=40; MPO-ANCA, n=126; PR3-ANCA, n=232). (A) PR3-ANCA seropositivity and (B) MPO-ANCA seropositivity are compared with ANCA seronegative cases. (C) MPO-ANCA seropositive and PR3-ANCA seropositive cases are compared. Data are presented as forest plots with the OR (x-axis, logarithmic scale) and 95% CI. ANCA, anti-neutrophil cytoplasmic antibody; ENT, ear, nose and throat; MPO, myeloperoxidase.
Figure 3
Figure 3
Kidney disease at diagnosis in paediatric-onset small vessel vasculitis stratified by ANCA status. A linear regression model was used to compare (A) kidney-specific disease activity, as measured by the renal pVAS (y-axis; median) (x-axis: ANCA-negative, n=43; MPO-ANCA, n=126; PR3-ANCA, n=232) and (B) kidney function, as measured by the eGFR (y-axis; median) (x-axis: MPO-ANCA, n=39; PR3-ANCA, n=84), at the time of diagnosis in children and adolescents with small vessel vasculitis. (C) An ordinal logistic regression model was used to compare the predicted probability (y-axis) of having (x-axis) normal kidney function (KDIGO stage 1, eGFR≥90), mildly reduced kidney function (KDIGO stage 2, 60≤eGFR≤89), moderately reduced kidney function (KDIGO stage 3, 30≤eGFR≤59), severely reduced kidney function (KDIGO stage 4, 15≤eGFR≤29) and kidney failure (KDIGO stage 5, eGFR<15) at diagnosis between MPO-ANCA (grey, n=39) and PR3-ANCA (black, n=84) seropositive AAV. All models were adjusted for age at diagnosis and sex as baseline variables. Data are presented as (A) boxplots with the median±IQR, (B) violin plots with the median (solid line) and IQR and (C) predicted probability±95% CI. AAV, ANCA-associated vasculitis; ANCA, anti-neutrophil cytoplasmic antibody; eGFR, estimated glomerular filtration rate; KDIGO, Kidney Disease Improving Global Outcomes; MPO, myeloperoxidase; pVAS, paediatric Vasculitis Activity Score.
Figure 4
Figure 4
Kidney disease trajectory from diagnosis to 1-year postdiagnosis in paediatric-onset AAV stratified by KDIGO stage at diagnosis and ANCA specificity. A linear mixed-effects model, adjusted for eGFR and age at diagnosis, alongside sex, was used to compare changes in kidney function, quantified using eGFR (y-axis) at the time of diagnosis, 6 months postdiagnosis and 12 months postdiagnosis (x-axis) between MPO-ANCA and PR3-ANCA seropositive paediatric patients with (A) normal to mildly reduced kidney function (KDIGO stages 1–2, eGFR≥60), (B) moderately reduced kidney function (KDIGO stage 3, 30≤eGFR≤59) or (C) severely reduced kidney function or kidney failure (KDIGO stages 4–5, eGFR≤29) at the time of diagnosis. (D) eGFR at diagnosis and 1-year postdiagnosis are also shown for a subset of participants with data availability who had severely reduced kidney function or kidney failure at diagnosis. Graphs are shaded to visualise KDIGO stages 1–2 (white), 3 (grey) and 4–5 (dark grey). Numbers in brackets on the x-axis (A–C) are individual patients. Data are presented as violin plots with the median (dotted line) and IQR. AAV, ANCA-associated vasculitis; ANCA, anti-neutrophil cytoplasmic antibody; eGFR, estimated glomerular filtration rate; KDIGO, Kidney Disease Improving Global Outcomes; MPO, myeloperoxidase.
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