Risk Factors Analysis for the Development of Hypocomplementemia in Rheumatoid Arthritis Patients: A Single-Center Retrospective Study

Figures & data

Table 1 Demographic and Serological Descriptors of RA Patients with HC and RA Patients Without HC

Index	RA with HC (n=78)	RA without HC (n=423)	P	Reference Range of the Index
Gender (male/female)	31/47	127/296	0.090
Age (years)	66.50(56.00–72.25)	62.00(55.00–69.00)	0.008
Age at onset (years)	56.00(43.50–67.00)	56.00(46.00–64.00)	0.721
Disease duration (months)	96.00(36.00–136.50)	48.00(12.00–120.00)	<0.001
Anti-CCP (RU/mL)	532.52(197.92–985.30)	480.25(70.20–992.76)	0.355	0–30
Anti-MCV (IU/mL)	643.98(180.23–1013.03)	322.17(69.29–955.99)	0.007	0–40
RF-IgA (IU/mL)	179.62(51.39–494.10)	80.82(9.05–343.21)	0.015	0–18
RF-IgG (IU/mL)	65.61(15.61–182.32)	43.41(6.25–100.12)	0.012	0–18
RF-IgM (IU/mL)	276.28(88.56–424.12)	206.80(34.11–316.57)	0.004	0–18
IgA (g/L)	3.21(2.33–4.64)	2.94(2.25–4.18)	0.263	0.7–4
IgG (g/L)	15.30(11.10–20.78)	13.42(11.20–18.68)	0.144	7–16
IgM (g/L)	1.58(1.01–2.08)	1.34(0.92–1.75)	0.019	0.4–2.3
CRP (mg/L)	23.81(7.85–57.98)	35.04(12.30–70.70)	0.090	0–5
ESR (mm/h)	61.00(37.75–93.00)	80.00(45.00–100.00)	0.024	0–15
WBC (10^9/L)	5.96(4.85–7.99)	7.16(5.64–8.91)	0.005	4–10
N (10^9/L)	4.49(3.15–5.68)	5.05(3.80–6.51)	0.015	2–7
N proportion (%)	70.25(63.05–79.55)	70.90(64.60–77.20)	0.989	50–75
L (10^9/L)	1.12(0.84–1.45)	1.31(0.98–1.73)	0.002	0.8–4.0
L proportion (%)	19.20(12.95–26.43)	19.00(14.10–24.70)	0.784	20–40
Hb (g/L)	104.50(89.75–119.50)	110.00(98.00–121.00)	0.029	Male (120–160) Female (110–150)
PLT (10^9/L)	238.50(171.00–309.50)	294.00(223.00–369.00)	<0.001	100–300
DAS28	6.02(5.31–6.30)	5.86(4.24–6.16)	0.006

Notes: The slash (/) represented “or” in gender, and the slash in the units represented “per”. P<0.05 represented statistical significance.

Abbreviations: RA, rheumatoid arthritis, HC, hypocomplementemia; Anti-CCP,anti-cyclic citrullinated peptide antibody; Anti-MCV, anti-mutated citrullinated vimentin antibody; RF, rheumatoid factor; RF-IgA, RF-IgG, RF-IgM, subtypes; IgA, IgG, IgM, immunoglobulins, CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; WBC, white blood cell; N, neutrophils; L, lymphocytes; Hb, hemoglobin; PLT, platelets.

Figure 1 Heat map of correlation clustering markers about the levels of C3, C4, Anti-MCV and other indexes in patients with RA.

Notes: Blue represented negative correlation, red represented positive correlation, and the color shade represented the strength of correlation. *P<0.05, **P<0.01.

Abbreviations: ESR, erythrocyte sedimentation rate; IgM, immunoglobulins; Anti-MCV, anti-mutated citrullinated vimentin antibody; RF, rheumatoid factor; RF-IgA, RF-IgG, RF-IgM, subtypes; PLT, platelets; N, neutrophils; WBC, white blood cell; C3,C4, complements; Hb, hemoglobin; L, lymphocytes.

Table 2 Correlation Analysis of C3, C4 and Other Indexes in Patients with RA

Index	C3		C4
	r	P	r	P
Age	−0.143	0.001	–	–
Disease duration	−0.138	0.002	–	–
Anti-MCV	−0.156	< 0.001	−0.241	< 0.001
RF-IgA	−0.090	0.044	−0.245	< 0.001
RF-IgG	−0.108	0.015	−0.309	< 0.001
RF-IgM	−0.136	0.002	−0.289	< 0.001
C3	–	–	0.428	< 0.001
C4	0.428	< 0.001	–	–
IgM	–	–	−0.202	< 0.001
ESR	0.201	< 0.001	–	–
WBC	0.222	< 0.001	–	–
N	0.209	< 0.001	–	–
L	0.189	< 0.001	0.116	0.009
Hb	0.090	0.044	–	–
PLT	0.265	< 0.001	–	–

Notes: r represented correlation coefficient, r (−1,1); “-” represented no correlation between two indexes. P<0.05 represented statistical significance.

Abbreviations: RA, rheumatoid arthritis; Anti-MCV, anti-mutated citrullinated vimentin antibody; RF, rheumatoid factor; RF-IgA, RF-IgG, RF-IgM, subtypes; C3,C4, complements, IgM, immunoglobulins; ESR, erythrocyte sedimentation rate; WBC, white blood cell; N, neutrophils; L, lymphocytes; Hb, hemoglobin; PLT, platelets.

Figure 2 Correlation network diagram about the levels of C3, C4, Anti-MCV and other indexes in patients with RA.

Notes: Circles of different colors and sizes represented the correlation degree of each index, with smaller circles and bluer colors indicating a lower degree of correlation, while larger circles and redder colors indicating a stronger degree of correlation; rho: the thickness of the arrow represented the magnitude of the correlation coefficient; relation: orange solid arrow represented positive correlation, gray dashed arrow represented negative correlation.

Abbreviations: ESR, erythrocyte sedimentation rate; IgM, immunoglobulins; Anti-MCV, anti-mutated citrullinated vimentin antibody; RF, rheumatoid factor; RF-IgA, RF-IgG, RF-IgM, subtypes; PLT, platelets; N, neutrophils; WBC, white blood cell; C3,C4, complements; Hb, hemoglobin; L, lymphocytes.

Table 3 Diagnostic Value of Anti-MCV, RF-IgM, PLT and Other Indexes in RA Patients with HC

	AUC (95% CI)	P	Cut-off Value	Sensitivity (%)	Specificity (%)	+LR	-LR	+PV	-PV	Youden index J
Age	0.60(0.55–0.64)	0.01	66.00	50.00	66.67	1.50	0.75	21.70	87.90	0.17
Disease duration	0.63(0.59–0.67)	<0.01	62.00	65.38	58.63	1.58	0.59	22.60	90.20	0.24
Anti-MCV	0.60(0.55–0.64)	<0.01	107.68	87.18	34.28	1.33	0.37	19.70	93.50	0.21
RF-IgA	0.59(0.54–0.63)	0.01	46.77	76.92	41.84	1.32	0.55	19.60	90.80	0.19
RF-IgG	0.59(0.55–0.63)	0.02	73.99	48.72	70.21	1.64	0.73	23.20	88.10	0.19
RF-IgM	0.60(0.56–0.65)	<0.01	316.57	44.87	75.18	1.81	0.73	25.00	88.10	0.20
IgM	0.58(0.54–0.63)	0.02	1.54	55.13	64.30	1.54	0.70	22.20	88.60	0.19
ESR	0.58(0.54–0.62)	0.02	69.00	60.26	57.21	1.41	0.69	20.6	88.60	0.17
WBC	0.60(0.56–0.64)	<0.01	5.97	51.28	68.79	1.64	0.71	23.3	88.40	0.20
N	0.59(0.54–0.63)	0.02	4.91	65.38	53.90	1.42	0.64	20.70	89.40	0.19
L	0.61(0.57–0.65)	<0.01	1.22	60.26	57.92	1.43	0.69	20.90	88.80	0.18
Hb	0.58(0.53–0.62)	0.04	99.00	43.59	72.81	1.60	0.77	22.80	87.50	0.16
PLT	0.65(0.60–0.69)	<0.01	305.00	75.64	47.99	1.45	0.51	21.10	91.40	0.24
DAS28	0.60(0.55–0.64)	<0.01	6.13	42.31	73.05	1.57	0.79	22.4	87.3	0.15

Notes: P<0.05 represented statistical significance.

Abbreviations: RA, rheumatoid arthritis; HC, hypocomplementemia; Anti-MCV, anti-mutated citrullinated vimentin antibody; RF, rheumatoid factor; RF-IgA, RF-IgG, RF-IgM, subtypes; IgM, immunoglobulins; ESR, erythrocyte sedimentation rate; WBC, white blood cell; N, neutrophils; L, lymphocytes; Hb, hemoglobin; PLT, platelets; AUC, the area under the receiver operating characteristic curve; +LR, positive likelihood ratio; -LR, negative likelihood ratio; +PV, positive predictive value; -PV, negative predictive value.

Figure 3 ROC curves analysis to evaluate the diagnostic value of Anti-MCV, ESR, PLT and other indicators for RA patients with HC.

Notes: Different colors represented different indicators. (A) ROC curves of anti-mutated citrullinated vimentin antibody (Anti-MCV), rheumatoid factor (RF) subtypes (RF-IgA, RF-IgG, RF-IgM), and immunoglobulins (IgM); (B) ROC curves of Age, Disease duration, erythrocyte sedimentation rate (ESR) and DAS28; (C). ROC curves of white blood cell (WBC), neutrophils (N), lymphocytes (L), hemoglobin (Hb) and platelets (PLT).

Table 4 Binary Logistic Regression Analysis of RA Patients with HC and Influencing Factors

Variables	Cut-off Value	Univariate Analysis			Multivariate Analysis
		OR	95% CI	P-value	OR	95% CI	P-value
Age	66.00	2.000	1.228–3.257	0.005	1.950	1.080–3.519	0.027
Disease duration	62.00	2.677	1.615–4.436	<0.001	2.287	1.284–4.076	0.005
Anti-MCV	107.68	3.547	1.773–7.096	<0.001	3.211	1.449–7.114	0.004
RF-IgA	46.77	2.398	1.369–4.203	0.002	1.412	0.676–2.948	0.358
RF-IgG	73.99	2.239	1.371–3.657	0.001	1.679	0.739–3.810	0.216
RF-IgM	316.57	2.465	1.499–4.055	<0.001	1.174	0.529–2.609	0.693
IgM	1.54	2.213	1.358–3.607	0.001	2.796	1.528–5.116	<0.001
ESR	69.00	2.027	1.239–3.318	0.005	5.737	2.657–12.387	<0.001
WBC	5.97	2.321	1.423–3.785	<0.001	1.075	0.432–2.673	0.876
N	4.91	2.209	1.334–3.656	0.002	1.552	0.637–3.780	0.333
L	1.22	2.087	1.275–3.416	0.003	1.222	0.647–2.307	0.536
Hb	99.00	2.070	1.260–3.399	0.004	3.289	1.650–6.555	<0.001
PLT	305.00	2.865	1.651–4.972	<0.001	2.719	1.367–5.409	0.004
DAS28	6.13	1.988	1.208–3.270	0.007	2.389	1.188–4.805	0.015

Notes: P<0.05 represented statistical significance.

Abbreviations: RA, rheumatoid arthritis; HC, hypocomplementemia; Anti-MCV, anti-mutated citrullinated vimentin antibody; RF, rheumatoid factor; RF-IgA, RF-IgG, RF-IgM, subtypes; IgM, immunoglobulins; ESR, erythrocyte sedimentation rate; WBC, white blood cell; N, neutrophils; L, lymphocytes; Hb, hemoglobin; PLT, platelets; OR, odds ratio; CI, confidence interval.