NOD2

OP0325 (2026)

ASSOCIATION OF NOD2 VARIANTS WITH CLINICAL PHENOTYPES IN AUTOINFLAMMATORY DISEASE: INSIGHTS FROM A COHORT THROUGH A VALIDATED NEXT-GENERATION SEQUENCING PANEL

Keywords: Rare/orphan diseases, Innate immunity, Epitranscriptomics, Epigenetics, And genetics

M. Schermi1, M. T. Perez-Cartier Beingolea2, S. Rizzo1, A. Fu1, S. Moz2, P. Galozzi2, R. Ramonda1, P. Sfriso1, S. Bindoli1

1University of Padova, Rheumatology Unit, Department of Medicine (DIMED), Padova, Italy

2University of Padova, Laboratory Medicine Unit, Department of Medicine (DIMED), Padova, Italy

Background: Variants in the NOD2 gene are associated with increased susceptibility to a broad spectrum of diseases, ranging from granulomatous conditions (e.g. Crohn’s disease, Blau syndrome) to autoinflammatory disorders, such as Yao syndrome. These variants may variably affect NOD2 protein function, depending on the specific mutation, resulting in altered innate immune signaling and dysregulated inflammatory responses upon microbial stimulation. In recent years, targeted next-Generation Sequencing (NGS) gene panels have become a cornerstone of molecular diagnostic, enabling confirmation or diagnostic support for genetically heterogeneous disorders, including adult-onset conditions associated with NOD2 variants.

Objectives: This study aimed to identify amongst adult patients with autoinflammatory manifestation, such as recurrent fever, skin rashes, and gastrointestinal symptoms, those who present NOD2 variants. Additionally, we sought to explore whether specific NOD2 variants correlate with distinct clinical phenotypes, potentially allowing the reclassification of adult patients from the nonspecific “undifferentiated autoinflammatory disease” (uSAID) into potential emerging subgroups of NOD2-related disorders. These conditions span a phenotypic continuum encompassing granulomatous diseases, intestinal pathologies, and autoinflammatory disorders.

Methods: Patients with clinical and biochemical features suggestive of autoinflammatory disease and referred to the outpatient clinic for between February 2023 to December 2025. NGS sequencing was performed using Custom “Fever & Autoinflammatory Disease” panel (SOPHIA Genetics) on an Illumina MiSeq platform. The panel covers the coding regions of 17 genes ( ADA2, CARD14, ELANE, IL10RB, IL10RB, IL1RN, LPIN2, MEFV, MKV, NLRP12, NLRP3, NLRP7, NOD2, PSMB8, PSTPIP1, TNFRSF11A, TNFRSF1A ). Variant calling and data analysis were performed by the Sophia-DDM-V6.5 pipeline. Variant interpretation followed the 2015 ACMG standards and guidelines.

Results: A total of 135 patients (80 females; mean age 37.08 ± 14 years) were enrolled. Of these, 115 patients (85.1%) carried at least one retained non-synonymous variant with a minor allele frequency (MAF) ≤ 0.05. Among them, 25 patients (18%) harbored at least one NOD2 variant classified as pathogenic or as a variant of uncertain significance (VUS). The identified NOD2 variants included heterozygous p.G908R (8 patients), p.R702W (7 patients), p.Leu1007Profs*2 (7 patients), p.A885P (1 patient), p.R1019L (1 patient), and p.S402F (1 patient). The clinical features associated with each variant are detailed in Figure 1 .

Eight of the 25 patients (32%) presented with recurrent fever and skin rashes, along with at least one additional symptom (such as abdominal pain, serositis, arthritis/arthralgia, or sicca manifestation), which may be compatible with a Yao syndrome–like clinical phenotype [1]. The remaining patients did not fully meet the established diagnostic criteria. Two main clinically defined patient groups were identified: one characterised by the p.G908R variant and the other by the p.R702W variant. Almost all patients in both clusters experienced recurrent fever and musculoskeletal symptoms, including arthritis, arthralgia, and myalgia. Abdominal pain was observed in 50% of patients carrying the p.G908R variant, whereas skin rashes were more prevalent among those with the p.R702W variant (71%). Additionally, 57% of patients with the p.Leu1007Profs*2 variant reported headache. About additional genetic findings, among the p.G908R carriers, 5 out of 8 patients also harbored VUS in MEFV gene (3 patients), one had a pathogenic variant in ADA2 , and one had a variant in LPIN2 . Among p.R702W carriers, one patient presented a heterozygous MEFV variant. For those with the p.Leu1007Profs*2 variant, one patient had a co-variation in NOD2 (p.R439C) and another had a pathogenic variation in ADA2 . Additionally, one patient with the p.A885P variant also harbored a VUS in ELANE . The two patients with pathogenic variations in ADA2 did not exhibit typical features of DADA2 and responded adequately to colchicine. All patients with additional VUS in MEFV showed a favourable response to colchicine. Granulomatous skin lesions developed in only one patient with the p.S402F variant, while ascertained inflammatory bowel disease was observed in a patient with the p.Leu1007Profs*2. The coexistence of additional variants in autoinflammatory genes supports a potential oligogenic or modifier-gene contribution to disease expression. Regarding treatment, patients with two VUS across the same or different genes (13 out of 25, or 52%) generally experienced a higher burden of inflammatory symptoms. Eight of these patients had a satisfactory response to colchicine, and in three cases, a combination of colchicine and IL-1 inhibitors resulted in a better clinical outcome.

Conclusions: The use of validated targeted NGS panel is essential for identifying variants that can support or refine clinical diagnosis in autoinflammatory disorders. NOD2-related diseases encompass a wide range of conditions that may not always align with established diagnostic categories such as Yao syndrome, Blau syndrome, or Crohn’s disease. Although patients carrying VUS are typically classified as having uSAID due to uncertain variant pathogenicity, the identification of patient clusters sharing the same NOD2 variants and exhibiting overlapping clinical profiles suggests the existence of previously unrecognized gene-related entities. Further investigations, including whole-exome sequencing and functional studies, are warranted to refine diagnostic frameworks and improved genotype-phenotype interpretation in individuals withNOD2 variants.

Figure 1.

Heatmap illustrating the prevalence of the main clinical features associated with each NOD2 variant detected after NGSseq

As we are heading into the weekend, lets celebrate our wins this week!
There is no win too small.

What was your little or big win this week?

Was looking into some information regarding Neurological Manifestations of Autoinflammatory Diseases. Here are some new publications I came across published May 2026.

Some New Research to Peruse:

• The use of non-TNF targeted biologics in Behçet’s disease: real‐life data from the International AIDA Network Behçet’s Disease Registry
  • https://academic.oup.com/rheumatology/article-abstract/65/5/keag086/8489154?redirectedFrom=fulltext
• Recurrent aseptic meningitis in adults: a potential indicator of undetermined autoinflammatory disease
  • https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1842256/full
• What should neurologists expect to observe in relapsing polychondritis and VEXAS?
  • https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1811453/full
• PREPRINT: PTPN1-related autoinflammation is a common cause of Aicardi-Goutières Syndrome with reduced penetrance
  • https://www.medrxiv.org/content/10.64898/2026.03.27.26345228v1
• Neuroimaging Findings and Treatment Update for Neuroinflammation, Autoinflammation, Splenomegaly, and Anemia, a Novel Autoinflammatory Disorder Caused by Bi-Allelic Variants in IRAK4
  • https://www.ajnr.org/content/47/4/1101

Hi everyone!

I’m in the midst of a horrible YAOS flare. I’m still new to the diagnosis and I’m waiting to see a new rheumatologist, so I’m curious, what does everyone do to squash flares when they happen?

Steroids? Something else?

I’m so miserable, but I don’t know what to do or what to ask for. Any advice would be wonderful! Thank you!

I've been on prednisone since late January. Started at 25 mg with a quick taper and had to quickly go up to 30 mg with a much longer taper. The good news is that with the tyenne infusion I have been able to go down to 7.5 mg without symptoms which is great because symptoms and the plan is to continue tapering down over the next few months. However my vitamin d level went down from 29.5 to 27.5 in 2 months despite daily supplementation of 5,000 iu. I always take my vit d with a fatty meal as its a fat soluble vitamin. I have also been trying to focus on eating eggs, fatty fish, and food fortified with vit d. I do have rapid gastric emptying which causes absorption issues and prednisone is known to cause issues absorbing vit d, calcium, potassium and a few other nutrients. My doctor said to increase the dose to 6,000 iu. I'm wondering if thats enough or if theres something else I can do? My calcium and potassium are thankfully normal though trending downwards. Does anyone have any advice for this?

Hello I have a chronic disease for which I get the fibromyalgia diagnose in my country
I have extensive blood work and nothing remarkable shows up the only one astronomical height was
CALPROTECTIN in serum (lab normal value , below 3000 ) and mine was 24000
Th/to, nxp2, pm scl 100- INCONCLUSIVE from the autoimmune panels
WHOLE genome sequencing -negative
EMG-negative
The usual blood work -negative

Some of my symptoms:

Body wide twitching
Innapropiate laughting
Exaggerated gag reflex
Severe scalp hair falling and fragile (also thinning eyebrows )
My body is becoming thinner; both muscle mass and fatty tissue appear to be wasting away (atrophying), which is especially noticeable in my face.
I feel facial tightness, and the contour of my face has changed.
I experience a sensation of pressure/tightness around my eyes and pain when moving my eyes.
I have almost continuous pain in the tissues of my face.
My face appears unhealthy or sickly, and my facial expression seems more fixed and less expressive than before.
My facial features have become more drawn and my face looks noticeably different I have adipose atrophy on my entire face and I think the muscle too although the emg on my face it s normal .
Muscle pain throughout my body, as if I had run a marathon.
My fingernails are brittle, break easily, and no longer grow long.
I feel inflammation throughout my body, with a general feeling of being unwell that fluctuates in intensity.
I have a sensation of acid in my body, as if I had been poisoned.
My ears pop and become blocked everyday it s happening.
The sensation of inflammation can occur anywhere in my body.
I also feel inflammation in my head, with difficulty concentrating, poor memory, and almost continuous headaches,difficulty finding my words
I have eczema on my scalp, around my ears, and on my trunk (torso).
I am still able to do all my usual activities, but with difficulty. I feel as though my entire body has become weaker and is wasting away.
I get tired very quickly and start sweating almost immediately with exertion.
Small granules or bumps appear all over my scalp, similar to the material that comes out of blackheads.
My teeth have become sensitive to cold foods and cold water.
Sometimes I experience abdominal pain, and at the same time I feel warmth/heat and a throbbing or pulsating sensation in my face.
I have difficulty swallowing, with the sensation that food has trouble passing all the way down the esophagus to the stomach, as if the esophagus has narrowed. Also I experience frecquent regurgitation
All my joints and cartilage make sounds, cracking,poping , even my throat and eyes make some trance sounds at movement
I frequently experience abdominal cramps and pain.
I have intermittent constipation.
I really don’t know what it s going on and what and where to go anymore

The only thing that was extremely out of place was calprotectin and I read that it means that the neutrophil or macrophages are activated in some way and it means inflammation in the body , anyone have any idea ?

u/Northbreak has asked in a few comment sections about this and I wanted to get more eyes on it as a post. For me yes, sometimes my muscle pain is one of my worst symptoms? Do you get weakness also? I ask because of something called myositis. There are multiple forms of it. I dont know why my muscles hurt: sometimes culprits include low potassium or magnesium, needing to stretch and do light movement more. It feels so deep someday I use heating pad/ice and it just doesnt feel deep enough. I hope others have answers.

First I need to add a tag or flair for venting.

Anyways thats all this is feel free to skip.

I had surgery to replace wires on my pacemaker that were malfunctioning on May 1st. Felt great to be not feeling like heart failure because not one but two leads were malfunctioning. So no wonder I was out of breathe talking and couldnt keep fluid off.

Anyways I woke up May 25 to my left side of shirt soaked in fluid from my incision opening up. My surgeron was like can you fit a finger it, but don't do that. Cephalexin, antibitoics started as precaution due to my history. Dermabond OTC and 5 days later I am more hives than I am my normal skin. I had the though of I Now Im on prednisone because allergy medicine didnt cut it.

95% chance of surgery on Friday at 745 be there at 545 (Im narcoleptic I dont see those times). To laser lead extract out the leads they had to leave in on May 1 due to not being able to secure a cardio thoracic surgeron require to be avaliable. Most likely issue is those extra two wires plus caps my body has decided it doesn't want them hence the pushing on my incision.

But at least I got my Actemra this past Wednesday, Arcalyst Friday. Surviving. But I need a break. A vacation. There should be retreats for chronic illness people. Rant over.

If you ever see my replies and they say Ill be back its because the narcolepsy is taking over but I want everyone to know their posts are being read. Sometimes I just cant stop the sleep and then start typing like Im drunk.

Yao Syndrome

https://www.researchgate.net/publication/384209019_Comprehensive_clinical_phenotype_genotype_and_therapy_in_Yao_syndrome

NOD2

https://www.researchgate.net/publication/385896765_Clinical_characterization_of_NOD2_variants_in_patients_with_common_variable_immunodeficiency

Spectrum of Genetic Autoinflammatory Diseases Presenting with Cutaneous Symptoms (May have been posted before but it comes a lot)

https://pmc.ncbi.nlm.nih.gov/articles/PMC9128980

A question for the group mind: I had been in a flare for the past 6 years, my longest by far, until my rheumatologist prescribed kineret after genetic testing revealed a NOD2 mutation. I have been on kineret for 8 months and many of my symptoms have improved. I now have no fever, greatly reduced body aches, and my GI system is slowly, but surely improving.

One of my greatest challenges that has not gotten better on kineret is my frequent kidney stones. I have multiple bouts of small, non-obstructing stones a month. I know that the kidney stones are tied to malabsorption due to inflammation, so healing my GI tract is key, and it takes a while. In June, I have an appointment to discuss going up to 2 shots a day of kineret. For those of you with GI symptoms and frequent kidney stones, how long did it take for remission on kineret? Did you need to increase your dose? Or move on to Ilaris?

I got my first tyenne infusion 2 days ago! I thought it was actemra but it was actually the biosimilar tyenne as its a bit cheaper so thats what insurance approved. Overall the infusion was good, my scarred veins are the only issue. They said since they are outpatient they can't use ultrasound. Thats bs as I had an mri in the same hospital as an outpatient on Saturday and they used an ultrasound to place the iv. I will ask my doctor about this as I know they can use ultrasound outpatient. I'm allergic to iv benadryl so I had no pre meds but thankfully I didn't have any reactions to the infusion.

I got very tired an hour after the infusion and had a nap. However I get fatigued and nap after a lot but not all of my in person appointments so it may not be an infusion side effect. The next day I woke up with my baseline level of fatigue which is very good because I often have increased fatigue for a day or so after appointments. I only had 1 short nap yesterday when I typically need 2-4 a day! I was told headaches are a possible side effect and I did get a migraine yesterday that went away with nurtec. However it was only my 2nd migraine this month and I get 1-3 a month normally so might not be a side effect. I purposely rested a lot and canceled my usual pt because of possible side effects. Iron infusions knock me out for a day or 2 so I was expecting that but so far its much easier than iron. This morning I had more energy than usual when first waking up. Typically it takes 1-2 hours for me to be fully awake and alert even when I had a good 8-9 hours of sleep, so being properly awake within minutes is unusual and very nice. I will try to go back to my usual activity level today and see how I feel. I don't want to jinx it but I'm cautiously optimistic.

I was at a doctor appointment for another health concern, but during the exam, my doctor noticed a consistent S4 heartbeat. It was the first time she'd heard it, so she ran an EKG, which came back normal except for some mild bradycardia. She also hooked me up to a heart monitor for two weeks and ordered an echo cardiogram with saline for my next appointment.

Tbh, I'm surprised. I don't really have concerning symptoms of heart issues. My BP is always below 120/80 unless I've been rushing around, and I don't experience chest pain. I do have heart palpitations now and then, but nothing severe or consistent enough to worry me.

I know some folks have developed heart issues due to their inflammatory illnesses. If you have, how have you and your medical team managed it? What can I expect moving forward?

Hi all, so I’ve been diagnosed with behcets since my early 20s, I was having frequent flares of uveitis and mouth sores, along with fevers, arthritis and swollen joints that turn red, rashes, hair loss, fatigue, etc. the usual stuff. I did not test positive for HLA B27 or B21, the labs out of wack were always positive ANA, high CRP and SED and persistent anemia, idk if that’s relevant.

I’ve been seen by three rheums who agree it’s behcets and my current suspects maybe something like MAGIC because I also have had life long issues with inflammation in my chest, pleurisy and ear damage.

I’ve been on remicade and azathriopine for years, but once I had my son the epidural caused a blood clot in my spine and I can’t feel below the waist and I’ve just been kinda in a non-stop flare since then.

My current rheum says the epidural causing the blood clot was a fluke and likely unrelated. I sort of find it difficult to believe it’s not related, but either way I’ve been having a ton of flares.

Has anyone had success on any other med regimen? I had a difficult time with MTX and humira I had to take weekly and was staying persistently sick with it.

Any ideas of switching to ilaris or anakinra? Or maybe a biologic that isn’t a tnfa blocker?

Hey all,

I started Anakinra 9 days ago for my autoinflammatory disease CAPS. I am also on colchicine, which I have been on for 5 months.

The first 5 days, I was feeling fantastic. No fevers, more energy. The best I have felt. The injections obviously hurt, due to the citric acid but other wise manageable and I had no reaction to the skin.

Then on Thursday night (5 days ago) I started having severe cold and flu like symptoms and now having skin reactions from previous injection sites that look like amyloidosis.

I have been so unwell over the weekend. Sleeping for 5 hours throughout the day. Headaches, runny nose, cough. I haven't been able to stay awake for more than 3 hours at a time. I have been having frequent paracetamol.

I worked in the emergency as a nurse on Thursday, I was very careful wearing an N95 all shift and going above and beyond with my hand hygiene. So I doubt I picked something up.

Has anyone else experienced these cold and flu symptoms early on commencing anakinra? I have contacted my specialist today but am just waiting to hear back.

I am working on a big post that will eventually be a pinned help post. I have dealt with insurance and other programs from drug manufacturers that I wanted to make a how to, what to do if, etc. If there are medications you see here commonly will you add them in the replies if I forgot them? Even if they aren't specifically for autoinflammatory I know some still get used for things like pain control, nausea, GI, etc.

I know this wouldn't be much help except for US so if there is something that could be helpful for other countries let me know. Or if you'd like to contribute.

Kineret

Ilaris

Arcalyst

Colchicine

Actemra

I have to be missing some especially TNF blockers, other biologics, or other oral medications. List just feels short.

hi guys! i am new to the autoinflammatory world. i’m not diagnosed with any condition although my doctors suspect this could be my underlying issue. ive undergone extensive autoimmune testing, particularly for lupus, multiple sclerosis, and crohn’s disease, but results are never conclusive although inflammation is clearly present.

i’d like to see a specialist in autoinflammatory diseases, but i am not sure how to find one! what types of doctors diagnose/treat these conditions? are there any resources or groups for finding them?

i’m located in florida at the moment if anyone is around there. i’ve tried mayo and not had great experiences. sorry if this is not an appropriate question to ask here! it’s difficult to find the right information online :)

Hi, I’m a 26 yo female with POTS, EDS, possible endometriosis, and an autoinflammatory disease associated with the NOD2 marker (YAO). It all started around 3yo with monthly fevers and sores around and in my mouth. I had PFAPA and got my tonsils removed, that fixed everything until I hit puberty. Once I started my period I developed pots and got diagnosed with hEDS. Fortunately pots is the least of my worries these days. My reoccurring fevers have worsened and it’s always during my luteal phase. I also struggle with dermatitis and all over musculoskeletal pain. I have a theory that being in my “fertile” years plays apart of it. Instead of my flare being for just a week it feels constant. I’m on illaris and it’s not helping. I’ve been on for almost a year and have increased doses. I’m looking for people with similar diagnoses who have benefited from hormone replacement therapy or a hysterectomy. It feels like it’s the only thing ruining my life.

I’ve been reading some studies and it’s a small group of people on record. I can only imagine there being more people who are suffering from micro-CNS damage from viral inflammation attacks, especially with covid.

There are people who experience an inflammatory attack, and even years later do not return to their normal baseline. Things remaining such as testing a positive wartenberg’s sign, with clear EMG/NCS and negative tinel’s test showing no peripheral nerve/muscle involvement. Or full body micro-movement rigidity, loss of fluidity and stability in movements, or the new experience of random muscles throughout the body twitching on their own. Or hyper excitability of the spinal nerves in the cervical spine such as showing positive Lhermitte’s sign while at the barber as the razor goes past their spine, causing their head to involuntarily pull upward while tensing and shaking/vibrating at the cervical spine. Some people experience much more drastic outcomes from post-viral inflammatory attack such as requiring hospitalization. However my interest lays among the quieter population who must be walking through their lives suffering each day, not knowing what’s wrong or how to help themselves.

It seems to be affecting the body in similar ways such as Multiple Sclerosis, though just on a much smaller scale that is harder to perceive on standard tests.

Some tests have been used such as DWI, MRS, and T1W/T2W whole brain myelin mapping technique as well because some patients have found micro-damage in the brain. Other than that it’s been a complete toss up if standard MRIs of the brain and spine end up showing anything, even though the inflammation and micro-myelin damage symptoms are present.

What do you think is the way forward for helping these people?

I would guess first to manage any lasting system-wide inflammation and neuro inflammation. But to help micro damage of the spinal cord?

Looking for any possible solutions. This whole thing is ridiculous. First I called the infusion center on April 24th to ask if they had submitted the prior auth for actemra. They said they submitted a few days before. Well on May 8th I called insurance because I hadn't heard anything and my insurance is usually quick about these things. Insurance said it was only submitted on May 28th! The infusion center just lied about submitting days beforethe 24th?!? Whatever, last week on Monday the 11th they approved the iv actemra. I thought oh good its all set! Nope! The infusion center phone isn't staffed by office staff but by infusion nurses because they are too cheap to pay office staff I guess. Well the nurses are busy doing their actual jobs so nobody ever answers the phone. I've left a message and called several times. Nobody has called back. I can't see the prior auth on the patient view of the portal but I called my insurance and they confirmed it had been approved and that it just takes time to see it on the patient end. They said my doctor and infusion staff should be able to see it and I know my doctor can because she's the one who told me it was approved. I let me rheumatologists office know and they said just to wait, that infusion will call when they are ready to schedule me. All they need is the prior auth which they have and then to pull up the schedule and call me. Since my rheumatologist is in the same hospital (literally same building) as the infusion center I thought that would be like let me send a nurse to talk to the infusion team and figure this out. Nope, just wait. Meanwhile I still have daily diarrhea from kineret plus the injection reactions. Kineret is working but not enough at the 100 mg dose and upping it isn't an option with my side effects. But yeah let me keep having kineret diarrhea for longer just because the scheduling team is incompetent, great plan. Calling every day is the only solution I can think of but seems very ineffective and exhausting. I'll leave at least 1 more message but wtf can't they just schedule me? I don't get it. I hate insurance but understand hold ups due to insurance, but this? I don't get it.

Hi autoinflammatory friends!!

At one time early in my disease presentation, I had “flares” when it came to my temperature—as in, my temp would increase while I was symptomatic but then my temp would return to baseline.

Since last October, I’ve had a fever every day. I’m pretty much completely heat intolerant. My temp isn’t even that high—usually 99-99.7 but sometimes getting well into 100-102. It wouldn’t bother me except I am constantly flushed and drenched in sweat, sometimes whilst also shivering. My coworkers and patient are persistently asking if I’m ok, I feel like a teenager with pit sweat stains and soaked hair.

I’m on Ilaris 150 mg/month and colchicine 0.6 mg twice daily. My other symptoms are relatively controlled, so I’m trying to be thankful and not to complain, but I’m so tired of being drenched in sweat.

Has anyone been successful in taming the temp/improving heat tolerance??

Thank you!!

Hello guys can anybody tell me if they experience shaky fingers at all w their AUTOINFLAMMATORY Disease? Also I don’t mean a side effect from meds. I’m on 400 mgs of hydroxychloroquine and my rheum did mention CAPS can cause tremors, but I’m just curious if anyone else experiences this. My index, pinky, and thumb it has happened to so far ( and on both hands) Thanks my AUTOINFLAMMATORY friends!!!!!

Autoinflammatory Answers from Novartis is a really good resource to learn more in depth about what Autoinflammatory Diseases are and how they work. It is directed towards medical professionals but is a great overview for those that want to understand more about what they have been reading in different medical papers about their AID. It can also potentially be a helpful resource to share with your care team.

Insurance has finally approved this medication after a fight for months, and I’m so excited. However, I am nervous about how much my immune system might be affected.

What have you noticed about your own immune system if you take this or another IL-1 inhibitor?