Add-On CICA Genetics
Add-On CICA Genetics profiles IL17F, TNF-α, and TGF-β1 gene variants from whole blood to identify inherited differences in cytokine regulation. Offered by Cell Science Systems as an adjunct to functional CICA testing, it informs inflammatory phenotype in autoimmune and chronic disease but is an exploratory tool, not a diagnostic genetic test;
3
Biomarkers
Blood (whole blood)
Sample
10–14 business days
Turnaround
No
Fasting
What is the CICA Genetics test?
Add-On CICA Genetics is a targeted genetic panel offered by Cell Science Systems that profiles single-nucleotide polymorphisms in three cytokine genes — IL17F, TNF-α, and TGF-β1 — known to modulate inflammatory and immune responses. It is ordered as an adjunct to the Cellular Innate and Cytokine Analysis (CICA) functional assay to provide a genetic layer of interpretation: whereas CICA measures ex vivo cytokine release in response to stimuli, the genetic add-on identifies inherited variants that may explain an individual's baseline inflammatory set-point and susceptibility to Th17-driven, TNF-mediated, or TGF-β-regulated disease. Practitioners use this add-on in patients with chronic inflammatory or autoimmune conditions where personalised mechanistic insight is sought — rheumatoid arthritis, inflammatory bowel disease, psoriatic arthritis, asthma, or unexplained systemic inflammation. The genetic results do not diagnose disease but inform phenotype, guide lifestyle and dietary interventions aimed at modulating inflammation, and in some cases support decision-making around biologic therapies, though pharmacogenetic evidence remains incomplete. This test is positioned within a functional-medicine or integrative framework and is not a standalone diagnostic genetic test.
What does the CICA Genetics test measure?
Interleukin 17F is a proinflammatory cytokine produced by Th17 cells that plays a central role in mucosal immunity and the pathogenesis of autoimmune and chronic inflammatory diseases. Genetic variants in IL17F modulate its biological activity and the magnitude of the inflammatory response; a specific functional polymorphism (His161Arg, rs763780) reduces IL17F signalling and has been associated with altered susceptibility to asthma, inflammatory bowel disease, and certain infections.
Identifying IL17F variants informs the practitioner's understanding of a patient's baseline inflammatory tone and responsiveness to Th17-driven pathways. Patients carrying the variant allele may exhibit a blunted IL17F response, which can alter disease phenotype and potentially influence therapeutic decisions in conditions where IL17 biology is central, such as psoriasis, ankylosing spondylitis, and Crohn disease.
Tumour necrosis factor alpha is a master proinflammatory cytokine secreted by macrophages and other immune cells, central to the systemic inflammatory response and implicated in the pathogenesis of rheumatoid arthritis, inflammatory bowel disease, and metabolic disorders. Polymorphisms in the TNF gene promoter region, notably −308G>A (rs1800629), influence transcriptional activity and circulating TNF-α levels; the A allele is associated with higher constitutive and stimulated TNF-α production.
Genotyping TNF-α variants helps stratify patients by their genetic predisposition to heightened inflammatory responses. Those with high-expression alleles may be more susceptible to TNF-driven autoimmune and inflammatory disease and could, in principle, derive greater benefit from anti-TNF biologics, though pharmacogenetic evidence remains incomplete and response is multifactorial.
Transforming growth factor beta 1 is a pleiotropic cytokine with both proinflammatory and regulatory functions, controlling T-cell differentiation, fibroblast activation, and extracellular matrix deposition. Genetic polymorphisms such as the +869T>C (Leu10Pro, rs1982073) and +915G>C (Arg25Pro, rs1800471) variants alter TGF-β1 secretion and signalling; some are associated with higher circulating levels and increased risk of fibrotic and autoimmune disease.
TGF-β1 variant status contributes to understanding an individual's susceptibility to fibrosis — in the lung, liver, and kidney — and to certain autoimmune conditions. High-secretor genotypes may predispose to excessive tissue remodelling and poorer outcomes in chronic inflammation, though clinical translation remains an area of active investigation.
Why is the CICA Genetics test ordered?
- Patients with established autoimmune or chronic inflammatory disease in whom understanding genetic inflammatory predisposition may refine management
- Individuals undergoing comprehensive immune profiling (typically with functional CICA testing) to correlate ex vivo cytokine release with underlying genetic architecture
- Assessment of TNF-α variant status when considering or optimising anti-TNF biologic therapy, recognising that pharmacogenetic utility is exploratory
- Investigation of fibrotic disease phenotype (pulmonary, hepatic, renal) where TGF-β1 genotype may contribute context, though not diagnostic
- Patients with recurrent infections or atypical inflammatory phenotype where IL17F variant status might explain blunted Th17 response
- Integrative or functional-medicine evaluation where genetic inflammatory markers are used to tailor anti-inflammatory dietary and lifestyle interventions
- Research or audit settings exploring genotype-phenotype correlations in inflammatory disease cohorts
Sample collection and turnaround
Sample type
Blood (whole blood)
Fasting required
No
Collection method
Venipuncture at patient service centre
Turnaround
10–14 business days
Collection notes
Phlebotomy at an approved draw site; whole blood collected in EDTA (lavender-top) tubes per Cell Science Systems protocol. Specimen handling and transit conditions must preserve DNA integrity; consult the laboratory's requisition for storage and shipping requirements.
Specimen requirements
Whole blood in EDTA tube, typically 3–5 mL. DNA extraction and genotyping are performed by Cell Science Systems; specimens are not interchangeable with other laboratories.
What can affect CICA Genetics results?
Whole-blood samples must be collected in EDTA tubes and stored according to the laboratory's protocol; haemolysis or prolonged transit can degrade DNA, though genotyping is generally robust to modest degradation.
Allele frequencies of IL17F, TNF-α, and TGF-β1 variants differ across populations, affecting the pre-test probability of carrying a given variant and potentially its phenotypic penetrance; interpretation should be ancestry-aware where evidence permits.
Genetic variants are probabilistic risk factors, not deterministic; actual cytokine levels and disease risk are modified by diet, microbiome, infection history, and other environmental exposures, so genotype alone does not predict phenotype.
Inflammatory phenotype is polygenic — many genes beyond IL17F, TNF-α, and TGF-β1 contribute — and epistatic interactions between loci are common, so single-variant interpretation has limited scope.
Cell Science Systems employs proprietary genotyping methods; results are not interchangeable with other platforms, and reference data are method-specific, limiting external comparability.
What do CICA Genetics results mean?
Elevated
Not applicable; genetic test results are genotypes (wild-type, heterozygous, homozygous variant), not quantitative elevations.
Normal
Homozygous wild-type for all three loci indicates the absence of the queried variants and suggests an average genetic predisposition to inflammatory cytokine production. It does not exclude inflammatory disease, which remains overwhelmingly multifactorial, nor does it guarantee protection from autoimmune or fibrotic conditions.
Reduced
Not applicable; genetic test results are genotypes, not quantitative reductions.
Note: Genotype results are descriptive, not diagnostic. A variant identified in IL17F, TNF-α, or TGF-β1 indicates an inherited difference in cytokine regulation that may — in the context of other genetic, environmental, and clinical factors — alter disease susceptibility or phenotype. Results should be integrated with functional CICA cytokine data, clinical history, and conventional inflammatory markers rather than interpreted in isolation. Practitioners should exercise caution in making therapeutic decisions based on genotype alone, as pharmacogenetic evidence for anti-TNF response remains incomplete and the clinical utility of IL17F and TGF-β1 genotyping is largely exploratory. Informed consent regarding genetic data privacy and the investigational nature of these markers is essential.
Frequently asked questions
The functional CICA test measures ex vivo cytokine release in response to stimuli, reflecting current immune activation. CICA Genetics profiles inherited variants in IL17F, TNF-α, and TGF-β1 genes that influence baseline inflammatory capacity. Together they distinguish genetic predisposition from environmental modulation.
How to access the CICA Genetics test
The CICA Genetics reference page is free and open to all practitioners. Create a free practitioner account to see pricing, save tests to your list, and generate requisition forms. Verification takes 1–2 business days.
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Published: October 7, 2026
Last reviewed: October 7, 2026
- Kawaguchi M, et al. IL-17F sequence variant (His161Arg) is associated with protection against asthma and antagonizes wild-type IL-17F activity. J Allergy Clin Immunol. (2006)
- Wilson AG, et al. Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc Natl Acad Sci USA. (1997)
- Grainger DJ, et al. Genetic control of the circulating concentration of transforming growth factor type beta1. Hum Mol Genet. (1999)
- McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol. (2007)
- Siebert S, et al. Cytokines as therapeutic targets in rheumatoid arthritis and other inflammatory diseases. Pharmacol Rev. (2015)
This content is for licensed healthcare practitioners only and does not constitute medical advice. Clinical decisions should be based on the full clinical picture and not on any single test result.