Warning: The following contains major spoilers for House of X #5, by Jonathan Hickman, Pepe Larraz, Marte Gracia, VC's Clayton Cowles and Tom Muller, on sale now.

The franchise-changing themes being established in Jonathan Hickman's House of X and Powers of X will have repercussions for not only the X-Men, but the entire Marvel Universe. As humans try to adjust to the new mutant status quo, superheroes will have to do the same, but with varying results.

We receive a glimpse of this in House of X #1, when Cyclops is confronted by the Fantastic Four. The tense standoff appears to foreshadow an eventual clash between the X-Men and Marvel's First Family, but another war is teased in House of X #5. This time, fans may expect the major revelation will lead to a sequel to the blockbuster 2012 crossover, Avengers vs. X-Men.

RELATED: House of X Reveals the Nations Against the X-Men (and Their Mutant Drugs)

After the United Nations pass a vote to allow the X-Men to establish a mutant sovereign nation, a data page highlights the countries that have rejected a trade treaty with Krakoa. The treaty is based on human nations and mutants reaching an agreement on the pharmaceutical drugs produced on Krakoa. While more than 100 nations have accepted a Krakoan trade deal, a small number decides mutant drugs aren't for them. In response, the X-Men categorize those countries as adversarial; the nation that stands out most is Wakanda, home of the Black Panther.

house of x infographic

Wakanda is a proud nation, and also one of the most advanced in the entire Marvel Universe, thanks to its Vibranium natural resource. "They do not need mutant drugs" is the notation on the Mutant Diplomacy infographic, which could simply mean Wakanda has no need for outside drugs when the nation is capable of taking care of its own citizens. However, it's the bright red highlight over the "Reason for Rejection" that makes us take pause.

House of X and Powers of X have used the red highlight as a sign of importance to alert readers. For example, all of the major revelations -- the Moira MacTaggert mutant retcon in House of X #2 and the mutant resurrections in House of X #5 -- were highlighted in red for the checklist found in each issue. Marvel clearly has plans to revisit Wakanda's stance, but what makes this a potential Avengers vs. X-Men II is Black Panther's current role as Avengers chairman.

RELATED: X-Men Theory: Marvel's New Xavier Is Secretly [SPOILER]

This new iteration of the Avengers brought back the Big 3 of Iron Man, Captain America and Thor, with Black Panther, Captain Marvel, Ghost Rider (Robbie Reyes), She-Hulk and Doctor Strange filling out the roster, although the Sorcerer Supreme left following the team's battle with the Celestials. Instead of assigning Iron Man or Captain America the leader of Earth's Mightiest Heroes, the members selected Black Panther as chairman. So if the X-Men should decide to take aggressive action against Wakanda, you can be sure Black Panther will bring the Avengers along as backup.

Avengers vs. X-Men was a 2012 blockbuster event that did exactly as the title suggests. The crux of the war revolved around the Phoenix Force returning to Earth to claim Hope Summers as its new host. While the X-Men saw the Phoenix/Hope merger as a positive sign for mutantkind, the Avengers treated the Phoenix as a threat that needed to be neutralized.

The Phoenix went on to possess Cyclops, Emma Frost, Namor, Colossus and Magik, transofrming them into the Phoenix Five. One of the major tragedies of Avengers vs. X-Men was Professor Charles Xavier's death at the hands of a Phoenix-possessed Cyclops. Tensions have understandably been high between both groups since then, but the rise of the X-Men is just the type of thing to reignite hostile feelings.

If the Avengers and X-Men rivalry returns, which side will suffer the greater loss? The X-Men have seemingly found a way to cheat death, which the Avengers will probably not look too kindly on. The big winner out of a sequel is the fans, as we'll get the chance to see our favorite heroes collide yet again.

KEEP READING: House of X: The Five X-Men Behind the Mutant Resurrection Machine