Science - USA (2022-04-08)

Perezet al.,Science 376 , eabf1970 (2022) 8 April 2022 3 of 13

cDC

pDC

cM

ncM

NK

Lymphoid B Myeloid

Prolif

CD4

UMAP1

UMAP2

CD8

PB

Progen

Lymphoid

Myeloid

A

UMAP1

UMAP2

B

European

CTL

European

SLE

Asian

CTL

Asian

SLE

1.0

0.8

0.6

0.4

0.2

0.0

Density

C cM ncM cDC pDC

NK Prolif PB Progen

CD4 CD8

B

Percentages

* * * **

* *

*

15

10

05

(^0000)
(^2020)
40
60
40
60

0. 5

1

2

2

4

40

60

20

0

(^00)
2
4
0 0 0
0.2
0.4

0. 5

1

20

40

10

20

LT

CE

EL

SE ACTL

EL

SA

LT

CE

EL

SE ACTL

EL

SA

LT

CE

EL

SE ACTL

EL

SA

LT

CE

EL

SE ACTL

EL

SA

LT

CE

EL

SE ACTL

EL

SA

LT

CE

EL

SE ACTL

EL

SA

LT

CE

EL

SE ACTL

EL

SA

LT

CE

EL

SE ACTL

EL

SA

LT

CE

EL

SE ACTL

EL

SA

LT

CE

EL

SE ACTL

EL

SA

LT

CE

EL

SE ACTL

EL

SA

cM ncM cDC pDC

NK Prolif PB Progen

CD4 CD8

B

CD4 cells

DE

Mono count (10

9 /L)

Lympho count (10

9 /L)

Case - Control percent change

European ancestry

10

0

0

-10

-10 10

-20

-20

yrt

se

cn

a

na

is

A

* *

ECTL ESLE ACTL ASLE

2.0

1.5

1.0

0.5

0.0

1.5

1.0

0.5

0.0

F

SLE effect size

= 0.39

P < 0.008

−0.05 0.00 0.05 0.10

−0.06

−0.04

−0.02

0.00

0.02

0.04

0.06

−0.10 −0.05 0.00 0.05 0.10

−0.04

−0.02

0.00

0.02

0.04

= 0.009

P < 0.92

Mono count effect size

Lympho count effect size

Fig. 1. Changes in composition of circulating immune cells in SLE.
(A) UMAP and assignment of 1.2 million cells to 11 cell types: classical and
nonclassical monocytes (cM and ncM); conventional and plasmacytoid
dendritic cells (cDC and pDC); CD4+and CD8+T cells (CD4 and CD8); natural
killer cells (NK); B cells (B); plasmablasts (PB); proliferating lymphocytes
(Prolif); CD34+progenitors (Progen). Subclustering of lymphoid (orange box)
and myeloid (blue box) cell populations. (B) Cell density plots of cases
and controls separated by ancestry. (C) Percentage (yaxis) versus case-
control status (xaxis) for each cell type separated by ancestry. Cell types with
significant percentage changes between cases and controls are highlighted.

*Padjusted< 0.05 [weighted least squares (WLS)]; blue bar indicates significant

meta-analysis by FisherÕs method. (D) Correlation in percentage change versus

controls between European (xaxis) and Asian (yaxis) cases. Colors are the

same as in (C). (E) Monocyte (top) and lymphocyte (bottom) abundances

(yaxes) versus case-control status (xaxis) from the UCSF EHR. Significant

differences between cases and controls are highlighted. *Padjusted< 0.05 (OLS).

(F) Scatterplot of effect sizes on SLE status (yaxis) versus effect sizes on

monocyte (top) or lymphocyte (bottom) abundance (xaxes) for genetic variants

associated with both traits reported ( 4 , 17 ). ECTL, European control; ESLE,

European case; ACTL, Asian control; ASLE, Asian case.

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