Table 4 The role of sCTLA-4 level in various chronic disease

SLE

21.6–12.3 ng/ml

(serum)

Elevated in SLE but does not correlate with disease activity.

[122]

4.05 (2.91–4.97) ng/mL (active SLE) dan 3.19 (1.73–4.67) ng/mL (non-active SLE)

(plasma)

Elevated in SLE and correlated with disease activity (SLEDAI score).

[82]

0–6326 pg/ml (median 1.044 pg/mL) (SLE)

0–4421 pg/ml (median 792.4 pg/ml) (healthy subjects)

(serum)

The level is very varying in SLE and healthy subjects.

[123]

19.58 ± 2.7 ng/ml

(serum)

Elevated in SLE.

[124]

RA

NA

(serum)

Elevate in RA and correlated with disease activity and treatment response.

[81]

4.4 ng/mL (4.3–4.7)

(serum)

Lower in RA compared with healthy subjects, higher in untreated RA rather than early RA patients but does not correlate with clinical condition.

[76]

2.25 ± 0.4 ng/ml

(serum)

Elevated in RA and correlated with inflammation joint count but does not correlate with laboratory test (ESR and CRP), HAQ score, and tender joint score.

[124]

Autoimmune thyroid disease (ATD)

9.8 ng/mL

(serum)

Elevated in autoimmune thyroid disease (Grave’s disease and autoimmune thyroiditis) but does not correlate with clinical manifestation.

[125]

28 to 78 ng/ml

(serum)

Elevated in ATD.

[126]

Grave’s disease

7.94 ng/mL

(serum)

Elevated in Grave’s disease but does not correlate with thyroid function nor Grave’s ophthalmology.

[127]

Myasthenia gravis

NA

(serum)

Elevated in myasthenia gravis and correlated with treatment response.

[83]

Neuromyelitis optica and multiple sclerosis

1.86 ± 1.13 ng/mL (neuromyelitis optica) dan 1.37 ± 0.88 ng/mL (multiple sclerosis)

(plasma)

Decreased in neuromyelitis optica and multiple sclerosis. There is no correlation with Expanded Disability Status Scale (EDSS) score in neuromyelitis optica and multiple sclerosis.

[84]

AAV

NA

(serum)

Decreased in AAV but does not correlate with treatment response.

[85]

Spondyl-arthropathy

3.66 ± 0.3 ng/ml

(serum)

Elevated in spondyloarthropathy and correlated with disease activity also CRP level.

[124]

Systemic sclerosis

> 26.5 ng/mL

(serum)

Elevated in diffuse cutaneous systemic sclerosis. Positively correlated with skin fibrosis width, serum IgG level, and anti-topoisomerase I antibody level.

[128]

Psoriasis vulgaris

4.045 ± 4.466 ng/mL

(serum)

Elevated in psoriasis vulgaris and correlated with disease Psoriasis Area Severity Index (PASI) score.

[129]

Celiac disease

0.0–96.4 ng/mL

(serum)

Increased in untreated celiac disease, correlated with gluten intake, mucosal damage degree, also disease activity.

[130]

Autoimmune disease

6.8ng/mL (RA), 6.34ng/mL (SLE),

8.75 ng/mL (overlapping autoimmune disease)

(serum)

Increased in SLE, RA, and overlapping autoimmune disease.

[131]

NA

(serum)

Increased in various autoimmune disease (autoimmune thyroid disease, celiac disease, primary biliary cirrhosis).

[132]

Asthma (adult)

2.8 (1.5–5.2) ng/mL (in non-steroid treatment), 2.9 (2.1–5.4) (in steroid treatment)

(plasma)

Increased in allergic asthma and correlated with serum total IgE.

[86]

20.2 ± 5.4 mg/L (atopic asthma), 19.2 ± 6.2 mg/L (non-atopic asthma)

(serum)

Elevated in atopy and non-atopy asthma, negatively correlated with forced expiratory volume, predicted peak expiratory, and PaCO₂, also positively correlated with lymphocytes count and disease severity.

[133]

Asthma (pediatric)

24.11 (15.19–24.33) ng/mL

(plasma)

Increased in allergic asthma but does not correlate with IgE level.

[87]

15.8 (11.3–19.2) ng/mL

(plasma)

Highly elevated in acute asthma attack, correlated with corticosteroid treatment response, negatively correlated with peak expiratory flow rate.

[88]

Mycobacterium tuberculosis infection

NA

(serum)

Elevated in serum TB patients.

[89]

Chronic HBV infection

NA

(serum)

Elevated in chronic HBV infection, correlated with ALT level, but not with AST level or disease activity (HbeAg level).

[90]

NA

(serum)

Decreased in HBV infection that has progressed to liver cirrhosis.

[108]

Alcoholic hepatitis

10 pg/mL

(plasma)

Decreased in alcoholic hepatitis and correlated with disease activity, bacterial translocation, and inflammatory parameters.

[109]

Abdominal aortic aneurism

NA

(plasma)

Decreased in abdominal aortic aneurism but does not correlate with age, aneurism size, or CRP level.

[98]

Endometriosis

75.53 pg/mL

(serum)

202.8 pg/mL (peritoneal fluid)

Increased in serum and peritoneal fluid of endometriosis stage III dan IV patients compared with stage I, II, or healthy subjects. But the level is higher in peritoneal fluid rather than in serum. Serum sCTLA-4 level has correlation with peritoneal fluid sCTLA-4 level.

[134]

Diabetic kidney disease

0.39 (0.28–0.51) ng/mL

(plasma)

Decreased in diabetic kidney disease.

[95]

Nephrotic syndrome

7.70 ± 1.2 pg/mL

(serum, rats)

9.64 ± 2.7 pg/mL

(urine, rats)

Increased in serum and urine of nephrotic syndrome rat. Urine sCTLA-4 positively correlated with total cholesterol, protein urine, and negatively correlated with serum albumin level.

[105]

MCD (pediatric)

458 ± 652 ng/g creatinine

(urine)

Increased in MCD relapse but does not correlate with treatment response.

[106]

ALL (pediatric)

132.0 ± 6208.7 ng/ml

(serum)

Elevated in active B-cell ALL and positively correlated with B cell leukemia percentage also potentially can be used as progression and disease severity marker.

[135]

Breast cancer

17.8 ± 5.9 ng/mL (preganglionic involvement)

17.2 ± 5.9 ng/mL (capsular invasion)

(serum)

Elevated in breast cancer with preganglionic involvement or with capsular invasion.

[93]

Gastric cancer

NA

(serum)

Elevated in gastric cancer.

[92]

HCC

NA

(plasma)

Elevated in HCC after trans arterial chemoembolization (TACE) but not in HCC after lenvatinib treatment.

[110]

≥ 30.5 pg/mL

(plasma)

Increased 2.64 fold in HCC after sorafenib treatment also correlated with sPD-L1 and sBTLA level.

[111]

Non-small cell lung carcinoma (NSCLC)

1.65 pg/mL

(serum)

Elevated in NSCLC especially in antibody-drug conjugate group.

[114]

Malignant Melanoma

> 200 pg/mL

(serum)

Elevated in malignant melanoma and correlated with best overall response (BOR) especially in immune-related stable or progressive disease, also correlated with ipilimumab treatment response.

[136]

NA

(serum)

Increased in melanoma and higher than in SLE or healthy subjects.

[33]