March 02, 2016

Enrollment in the Natural Killer T-cell (NKT) Study

As of March 2015:

121 participants with sarcoidosis

64 participants without sarcoidosis

612 follow-up visits (participants returning at 6-month intervals)


Enrollment in the GRADS Study

As of study completion, August 2015:

60 participants with sarcoidosis

15 participants with Alpha-1 antitrypsin deficiency


None of the work we have accomplished so far could have been done without our participants! Because of these studies, we are closer to understanding how a new type of T cell is regulated in sarcoidosis, and we are currently doing studies to understand the function of this T cell in sarcoidosis. In addition, we are performing experiments to identify blood markers that might track with clinical symptoms such as fatigue, shortness of breath, cough or neurological symptoms.

March 02, 2016

Dear Study Participants,

We want to sincerely thank you for your participation in the ongoing sarcoidosis studies and second, update you on the progress we have made in better understanding sarcoidosis. Without your participation, we would not have the knowledge we have today.

Research Findings

  • In our last few letters, we informed you about the progress we are making in understanding how natural killer T cells in the blood show evidence of "exhaustion" in their ability to make inflammatory products. We are continuing to study these cells by looking at whether they migrate to the lung in sarcoidosis patients compared to control subjects. Since there are medications that can turn on these natural killer T cells it is essential that we figure out if they are "good" or "bad" in making sarcoidosis inflammation before using the medications.
  • We also told you about an exciting finding relating to a blood marker that predicted which subjects showed decline in their lung function and which did not. Well to get something like this into the clinic, we MUST validate it in another NEW group of patients. So we are continuing our study and enrolling additional subjects to participate. IN ADDITION, because we, at UCSF, are the NIH site for recruitment into the GRADS study, we will be able to use samples collected as part of the GRADS study, which some of you may have participated in. All this is very exciting and necessary steps to get closer to a blood marker that we can use in the clinic.
  • We are working on applying for additional funding to push this finding further, understand the biology of the blood marker, called CXCL9, and our goal is by doing so, we may find new "targets" in sarcoidosis therapy.

Finally, the GRADS study will be ending on June 30th, 2015. We will be working with the NIH to analyze the information and samples collected, so this year is looking very fruitful!

What is new?

Exciting news on the clinical trials front! We were awarded funds to perform a clinical trial looking at a medication called Acthar. This medication is FDA-approved for sarcoidosis, and the goal is to figure out which patients will best benefit from it. We anticipate that we will have approval to start enrolling in early 2016.

What can we do with this information?

These discoveries are really important for many reasons:

  • Sarcoidosis needs non-invasive diagnostic tests. Work using blood to identify unique "signatures" is one way we think that we can find a way to get closer to a "blood test" for sarcoidosis.
  • Discoveries such as CXCL9 represent important biological tools for pharmaceutical companies as they perform clinical trials and can use these biomarkers to assess the patient response to a therapy. This is the goal with the industry-related clinical trial mentioned above.
  • Discovering the importance of CXCL9 in the disease course of sarcoidosis also opens up an entire area of study which may identify additionally important biomarkers that also could be targets for new therapies.
  • These findings give us hope that in the future we will have several biomarkers to use in clinical practice and new drugs focused on these new biomarkers with the goal of decreasing side effects of therapy.
  • These findings can help educate doctors about the symptoms that patients with sarcoidosis suffer from so they may be better in finding ways to alleviate the suffering.

The goal we are all working for is to find a cure and stop the suffering!

Where are we going from here?

  • We have reached a big milestone in our study and have a better understanding about the visit time points that appear to be very useful. We have found that the most critical time points for the blood samples are at the first visit, year 1 and year 2. We do not yet have enough study participant visits at the 5 year time point so we would like to continue this time point and hope that participants stay involved.
  • Also we think another very important study is the relapse or flare study. So little is known about why sarcoidosis symptoms suddenly worsen that this work really needs to be done to understand and have any hope to have better treatments.

We hope to grow our clinical trials program once we have the experience from this first trial. There are many biologic medications out there and our research is showing rationale to use them in sarcoidosis.

As a team, we are making great strides in pushing the field forward. Thank you for your time and dedication to this research effort!

March 02, 2016

We would like to thank all of our subjects who have participated in our ongoing studies. Nothing could have been accomplished without your involvement!

Research Findings

  • First, we have identified that specific cells of the immune system, called natural killer T cells, are very low in the circulation of patients with sarcoidosis.
  • We have also identified that these cells do not function well in sarcoidosis.
  • We have linked this abnormal function to a molecule that has been shown to dampen the function of T cells generally. This finding is important because there are experimental medications that block this molecule and future studies may be able to study this medication in sarcoidosis.
  • We have also identified that there are different inflammatory patterns activated in patients with sarcoidosis (we are now trying to do more studies to understand what this means in terms of whether sarcoidosis resolves or continues to be active).
  • We have identified that many patients with sarcoidosis have multiple neurologic symptoms and symptoms of depression. These findings are going to be further studied by a neurologist at UCSF who has a special interest in neurosarcoidosis.

What can we do with this information?

These discoveries are critically important for many reasons:

  • They improve awareness of the biological processes that are altered in sarcoidosis so that drug companies can find new medications to beat the inflammation in sarcoidosis.
  • They give us hope that in the future we might have better tests to diagnose sarcoidosis as well as help doctors figure out which patients might go on to have more severe forms of disease, so they can act earlier and monitor patients better.
  • These findings can help educate doctors about the symptoms that patients with sarcoidosis suffer from so they may be better in finding ways to alleviate the suffering.
  • These findings also show researchers where to focus their efforts in future studies to understand the disease.The goal we are all working for is to find a cure and stop the suffering!

Where are we going from here?

  • Because we have discovered so much this far, we are planning to continue the study to collect samples and clinical information.
  • We were just awarded a grant which will allow us to study relapses or "flares" of sarcoidosis.
  • We would also like to work towards organizing a "Sarcoidosis Education Seminar" for patients and study participants.
  • We are also one of 7 research centers across the US that have been asked to participate in the NIH-funded study called "GRADS" which is trying to understand the link between microorganisms and sarcoidosis. More information about this study can be found at this website:
February 26, 2016

Su, Robert, Michael M. Li, Nirav R. Bhakta, Owen D. Solberg, Eli PB Darnell, Joris Ramstein, Suresh Garudadri, Melissa Ho, Prescott G. Woodruff, and Laura L. Koth. Longitudinal analysis of sarcoidosis blood transcriptomic signatures and disease outcomes. European Respiratory Journal 44, no. 4 (2014): 985-993.

Su, Robert, M. L. Nguyen, Misha R. Agarwal, Christopher Kirby, Christine P. Nguyen, Joris Ramstein, Eli P. Darnell, Antonio D Gomez, Melissa Ho, Prescott G. Woodruff, and Laura L. Koth. Interferon-inducible chemokines reflect severity and progression in sarcoidosis. Respir Res 14, no. 1 (2013): 121.

Snyder-Cappione JE, Nixon DF, Chi JC, Nguyen ML, Kirby CK, Milush JM, Koth LL. Invariant Natural Killer T (iNKT) Cell Exhaustion in Sarcoidosis. Eur J Immunol. 2013 May 10.

Koth LL, Solberg OD, Peng JC, Bhakta NR, Nguyen CP, Woodruff PG. Sarcoidosis Blood Transcriptome Reflects Lung Inflammation and Overlaps with Tuberculosis. Am J Respir Crit Care Med. 2011 Aug 18.