The study is designed to learn more about the causes of rheumatoid arthritis (RA). People who get RA have elevated protein markers called autoantibodies in their blood years before initial symptoms of arthritis. The goal of this study is to learn more about how autoantibodies in RA might be related to inflammation in the lungs.

The Specific Aims of This Study Are As Follows:

1. Identify whether sputum anti-CCP predicts incident RA
2. Determine the effect of inflammatory cytokines on the induction of NETosis in sputum neutrophils
3. Determine the role of sputum macrophage phagocytosis in NET clearance <br> The knowledge gained from this study will improve the overall understanding of the development of RA. It is anticipated that these findings will improve the field's understanding of how best to screen for RA risk and target RA prevention. This study could support future lung-targeted prevention strategies for RA that could avoid the administration of systemic toxic therapies. Such potential prevention interventions could be implemented in subjects at risk for RA in order to prevent the irreversible joint damage that can occur in the later stages of clinically-apparent RA.

Inclusion Criteria:

• Adults between 18 and 100 years;
• At-Risk for RA, RA diagnosed, and Healthy Control subjects will be included in the study until recruitment goals are met for each group.

At-Risk:

1. No evidence of inflammatory arthritis on clinical examination AND

2. At elevated risk for RA based on familial or serologic risk

   • Familial risk includes having a first degree relatives (FDRs) with RA
   • Serologic risk includes asymptomatic serum ACPA positivity

Healthy Controls :

1. No history of RA
2. No FDRs with RA
3. No systemic use of immunosuppressants for autoimmune disease

RA Diagnosis:

1. Classified RA by 1987 ACR and/or 2010 ACR/EULAR RA classification criteria (confirmed by medical chart review) OR
2. Diagnosed with RA by a board-certified rheumatologist (confirmed by medical chart review)

Exclusion Criteria:

1. Currently pregnant or planning to become pregnant during the sample collection period of the study
2. Exacerbation of underlying obstructive lung disease within the past 1 month
3. Known FEV1 <1 liter
4. Oxygen requirement >2 liters at rest
5. Participants with health acuity or behavioral health concerns leaving them unable to participate in the current research

Note: If a subject temporarily does not meet inclusion criteria but is interested in participating, he/she may participate once inclusion criteria have been met.

If interested, please take a few minutes to complete the screening questionnaire for this study opportunity. You may open the survey in your web browser by clicking the link below:

https://is.gd/SPAROscreen

If the link above does not work, try copying the link below into your web browser:

https://redcap.ucdenver.edu/surveys/?s=3WM8WH3WKK

We will recruit subjects from 1) the Denver site of the SERA project (COMIRB #01-0675); 2) local rheumatology clinics, including the University of Colorado Hospital (UCH), Denver Health, National Jewish Health (NJH), and the Denver Arthritis Clinic; 3) local health clinics at UCH; and 4) local advertisements.