Table 1.

Soluble immune markers and their role in diseases

Soluble Immune Markers	Role in Diseases
sCTLA‐4	1. Elevated in sera of autoimmune diseases (autoimmune thyroiditis, lupus, myasthenia gravis, and systemic sclerosis),33, 34, 35, 36 inflammatory diseases (celiac disease and allergic asthma), and B‐cell acute lymphoblastic leukemia (B‐ALL).12 2. Higher serum levels are suggested to be a risk factor in type 1 diabetes.37 3. Can be used as an important prognostic marker in breast cancer,13 esophageal cancer, and pleural mesothelioma.11
Soluble B7 ligands	1. sB7‐2 is elevated in sera of acute myeloid leukemia (AML) that correlates with lower survival rates54; it is also a prognostic marker in myeloma patients.53 2. sB7‐H3, elevated in the sera, indicates poor prognosis in non‐small‐cell lung cancer (NSCLC).58 3. sB7‐X is detected in sera of renal cell carcinoma (RCC) patients62 and also correlates with advanced tumor staging.61
sCD28	Increased serum level is associated with disease severity in autoimmune diseases like lupus,44 Sjogren syndrome,44 and systemic sclerosis44 and also can be used as a biomarker in breast cancer.45
sPD‐1	Elevated levels in the sera—found in autoimmune diseases106; correlates to cancer progression; correlates with sustained high hepatitis B viral load and increased risk of hepatocellular carcinoma109; found in classical Hodgkin lymphoma (CHL).110
sPD‐L1	Elevated in the sera of renal cell carcinoma (RCC),100 myeloma,101 and B‐cell lymphoma patients102 and can be used as a prognostic marker.
sCD226	Serum CD226 increases and interacts with tumor cell expressed CD155 in cutaneous T‐cell lymphoma.138
sCD40	Elevated in pleural effusion of non‐small‐cell lung cancer (NSCLC) patients that correlates with poor prognosis and disease advancing145; also increased in sera of uremic patients and inhibits B‐cell response.148, 149
sCD40L	Elevated levels in sera—correlates with immunosuppression in cancer150; found in patients with lung adenocarcinoma and also associated with distant metastasis151; found in pancreatic ductal adenocarcinoma (PDAC) patients152; found in chronic lymphocytic leukemia (CLL)153; involved in acute coronary syndromes154, 155; found in HIV patients.156
sOX40	Elevated in the sera of patients with chronic lymphocytic leukemia as compared with healthy patients.157
s4‐1BB	Elevated in colorectal cancer patients with tumor localized in the colon.158
s4‐1BBLs	Elevated in the sera of patients with several hematological malignancies like acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and in non‐Hodgkin lymphoma (NHL).147
sCD27	Elevated in the sera of cancer patients.159
sGITR	Elevated in the sera of patients with primary Sjogren syndrome, an autoimmune disease.160